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Protective Effect of Tangshen Formula on interstitial cells of cajal in Colon of Diabetic Rats

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Chinese Journal of Integrative Medicine 2022年第1期28卷 43-51页

作者： CHEN Peng-min ZHAO Jing-bo YANG Xin LI Jing ZHANG Hao-jun ZHANG Hui-cun ZHANG Yu-ting LI Ping Beijing Key Lab Immune-Mediated Inflammatory Diseases Institute of Clinical Medical SciencesChina-Japan Friendship HospitalBeijing(100029)China Department of Clinical Medicine Aarhus UniversityAarhus(8200)Denmark Department of Combination of Traditional Chinese and Western Medicine Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing(100010)China

Objective:To explore the effect of Tangshen Formula(TSF),a Chinese herbal medicine,on interstitial cells of cajal(ICC)in the colon of diabetic ***:Fifty-four male Wistar rats were randomly divided into normal control(NC,n=14)and high-fat diet(HFD)groups(n=40).After 6 weeks,the rats in the HFD group were injected intraperitoneally streptozotocin once(30 mg/kg).Thirty rats with fasting blood glucose higher than 11.7 mmol/L were randomly divided into diabetes(DM)and TSF groups,15 rats in each *** in the NC and DM groups were intragastrically administered with saline,and those in the TSF group were given with TSF(2.4 g/kg)once daily for 20 *** levels of Bax,Bcl-2,and caspase-3 in colonic smooth muscle layer were measured by Western blotting and immunohistochemical *** number of ICC was determined by immunohistochemical *** was used for analyzing the ratio of classically activated macrophages(M1)and alternatively activated macrophages(M2)to total *** microscopy was used to observe the epithelial ultrastructure and ***:TSF appeared to partially prevented loss of ICC in DM rats(P<0.05).Compared with the NC group,expression levels of Bcl-2,Bax,caspase-3,and TNF-αas well as the ratio of M1 to total macrophages increased in DM rats(all P<0.05),and the ratio of M2 to total macrophages decreased(P<0.05 or P<0.01).Compared with the DM group,TSF decreased the expression levels of abovementioned proteins and restore M2 to total macrophages ratio(P<0.05 or P<0.01).TSF appeared to attenuate the ultrastructural changes of epithelia and improve the tight and desmosome junctions between epithelia reduced in the DM ***:Reduced number of ICC in DM rats may be associated with damage of the intestinal *** protective effects of TSF on ICC may be through repair of the epithelial junctions,which attenuates inflammation and inflammation-initiated apoptosis in colon of DM rats.

关键词： diabetes interstitial cells of cajal tight junction intestinal epithelia macrophage Tangshen Formula

Identification of TRPM7 channels in human intestinal interstitial cells of cajal

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World Journal of Gastroenterology 2009年第46期15卷 5799-5804页

作者： Byung Joo Kim Kyu Joo Park Hyung Woo Kim Seok Choi Jae Yeoul Jun In Youb Chang Ju-Hong Jeon Insuk So Seon Jeong Kim School of Korean Medicine Pusan National University Department of Surgery College of MedicineSeoul National University Department of Physiology College of MedicineChosun University Department of Anatomy College of MedicineChosun University Center for Bio-Artif icial Muscle and Department of Physiology College of MedicineSeoul National University Center for Bio-Artifi cial Muscle and Depart-ment of Biomedical Engineering Hanyang University

AIM： To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 （TRPM7） in the human gastrointestinal （GI） tract. METHODS： Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajat （ICCs）. RESULTS： The human GI tract generated slow electrical waves and had ICCs which functioned as pacemak er cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB （2-aminoethoxydiphenyl borate） and La3＋, TRPM7 channel blockers, inhibited the slowwaves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION： These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the gen- eration of the slow waves.

关键词： Electrophysiology interstitial cells of cajal TRPM cation channels Transient receptor potential melastatin-type 7 protein Human Gastrointestinal tract

Different distributions of interstitial cells of cajal and platelet-derived growth factor receptor-α positive cells in colonic smooth muscle cell/interstitial cell of cajal/plateletderived growth factor receptor-α positive cell syncytium in mice

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World Journal of Gastroenterology 2018年第44期24卷 4989-5004页

作者： Chen Lu Xu Huang Hong-Li Lu Shao-Hua Liu Jing-Yu Zang Yu-Jia Li Jie Chen Wen-Xie Xu Department of Physiology Shanghai Jiao Tong University School of Medicine Department of Anesthesiology Ren Ji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Department of Pediatric Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

AIM To investigate the distribution and function of interstitialcells of cajal(ICCs) and platelet-derived growth factor receptor-α positive(PDGFRα+) cells in the proximal and distal *** The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes(CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread. Intracellular recordings were used to assess electrical field stimulation(EFS)-induced inhibitory junction potentials(IJP) on the colonic smooth muscle. Western blot analysis was used to examine the expression levels of ICCs and PDGFRα in the colonic smooth *** Treatment with NG-nitro-L-arginine methyl ester hydrochloride(L-NAME) significantly increased the CMMC frequency and spontaneous contractions, especially in the proximal colon, while treatment with MRS2500 increased only distal CMMC activity and smooth muscle contractions. Both CMMCs and spontaneous contractions were markedly inhibited by NPPB, especially in the proximal colon. Accordingly, CyPPA sharply inhibited the distal contraction of both CMMCs and spontaneous contractions. Additionally, the amplitude of stimulationinduced nitric oxide(NO)/ICC-dependent slow IJPs(sIJPs) by intracellular recordings from the smooth muscles in the proximal colon was larger than that in the distal colon, while the amplitude of electric field stimulationinduced purinergic/PDGFRα-dependent fast IJPs(fIJPs) in the distal colon was larger than that in the proximal colon. Consistently, protein expression levels of c-Kit and anoctamin-1(ANO1) in the proximal colon were much higher, while protein expression levels of PDGFRα and small conductance calcium-activated potassium channel 3(SK3) in the distal colon were much *** The ICCs are mainly distributed in the proximal colon and there are more PDGFRα+ cells are in the dis

关键词： interstitial cells of cajal Platelet-derived growth factor receptor-α positive cells Smooth muscle cell/interstitial cell of cajal/platelet-derived growth factor receptor-α positive cell syncytium Nitric oxide Purine

Hwangryunhaedok-tang induces the depolarization of pacemaker potentials through 5-HT3 and 5-HT4 receptors in cultured murine small intestine interstitial cells of cajal

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World Journal of Gastroenterology 2017年第29期23卷 5313-5323页

作者： Hyun Jung Kim Guem San Lee Hyungwoo Kim Byung Joo Kim Division of Longevity and Biofunctional Medicine Healthy Aging Korean Medical Research Center School of Korean Medicine Pusan National University Wonkwang University College of Korean Medicine Division of Pharmacology School of Korean Medicine Pusan National University Division of Longevity and Biofunctional Medicine School of Korean Medicine Pusan National University

AIM To investigate the effects of a water extract of Hwangryunhaedok-tang(HHTE) on the pacemaker potentials of mouse interstitial cells of cajal(ICCs).METHODS We dissociated ICCs from small intestines and cultured. ICCs were immunologically identified using an antic-kit antibody. We used the whole-cell patch-clamp configuration to record the pacemaker potentials generated by cultured ICCs under the current clamp mode(I = 0). All experiments were performed at 30 ℃-32 ℃RESULTS HHTE dose-dependently depolarized ICC pacemaker potentials. Pretreatment with a 5-HT_3 receptor anta-gonist(Y25130) or a 5-HT_4 receptor antagonist(RS39604) blocked HHTE-induced pacemaker potential depolarizations, whereas pretreatment with a 5-HT7 receptor antagonist(SB269970) did not. Intracellular GDPβS inhibited HHTE-induced pacemaker potential depolarization and pretreatment with a Ca^(2+)-free solution or thapsigargin abolished the pacemaker potentials. In the presence of a Ca^(2+)-free solution or thapsigargin, HHTE did not depolarize ICC pacemaker potentials. In addition, HHTE-induced pacemaker potential depolarization was unaffected by a PKC inhibitor(calphostin C) or a Rho kinase inhibitor(Y27632). Of the four ingredients of HHT, Coptidis Rhizoma and Gardeniae Fructus more effectively inhibited pacemaker potential *** These results suggest that HHTE dose-dependently depolarizes ICC pacemaker potentials through 5-HT_3 and 5-HT_4 receptors via external and internal Ca^(2+) regulation and via G protein-, PKC-and Rho kinase-independent pathways.

关键词： Hwangryunhaedok-tang interstitial cells of cajal Pacemaker potentials Gastrointestinal tract Motility

Characterization of smooth muscle, enteric nerve, interstitial cells of cajal, and fibroblast-like cells in the gastric musculature of patients with diabetes mellitus

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World Journal of Gastroenterology 2016年第46期22卷 10131-10139页

作者： Kyung Sik Park Kwang Bum Cho Il Seon Hwang Jae Hyung Park Byung Ik Jang Kyeong Ok Kim Sung Woo Jeon Eun Soo Kim Chang Sik Park Joong Goo Kwon Department of Internal Medicine Keimyung University School of Medicine Department of Pathology Keimyung University School of Medicine Department of Physiology Keimyung University School of Medicine Department of Internal Medicine Youngnam University College of Medicine Department of Internal Medicine Kyungpook National University School of Medicine Department of Advanced Materials Convergence Korea Institute of Ceramic Engineering and Technology Department of Internal Medicine Catholic University of Daegu School of Medicine

AIM To investigate histologic abnormalities in the gastric smooth muscle of patients with diabetes mellitus(DM).METHODS Full-thickness gastric specimens were obtained from patients undergoing surgery for gastric cancer. H&E stain and Masson's Trichrome stain were performed to assess the degree of fibrosis. Immunohistochemical staining using various antibodies was also performed [antibodies against protein gene product 9.5(PGP9.5), neuronal nitric oxide synthase(n NOS), vasoactive intestinal peptide(VIP), neurokinin-1(NK1) receptor, c-Kit, and platelet-derived growth factor receptor-alpha,(PDGFRα)]. Immunofluorescent staining and evaluation with confocal microscopy were also *** Twenty-six controls and 35 diabetic patients(21 shortduration patients and 14 long-duration patients) were included. There were no significant differences in basic demographics between the two groups except in mean body mass index(BMI)(higher in the DM group). Proportions of moderate-to-severe intercellular fibrosis in the muscle layer were significantly higher in the DM group than in the control group(P interstitial cells of cajal(ICC) was observed to decrease with increasing duration of *** Our study suggests that increased intercellular fibrosis, loss of ICC, and loss of fibroblast-like cells are found in the smooth muscle of DM patients. These abnormalities may contribute to changes in gastric motor activity in patients with DM.

关键词： Diabetes mellitus interstitial cells of cajal Fibroblast-like cell Gastroparesis Enteric nerve system

Xiangbinfang granules enhance gastric antrum motility via intramuscular interstitial cells of cajal in mice

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World Journal of Gastroenterology 2021年第7期27卷 576-591页

作者： Qi-Cheng Chen Zhi Jiang Jun-Hong Zhang Li-Xing Cao Zhi-Qiang Chen The Research Team of TCM Applications of Perioperative The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangdong Provincial Hospital of Traditional Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Department of Research Public Service Center The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangdong Provincial Hospital of Traditional Chinese MedicineGuangzhou 510120Guangdong ProvinceChina

BACKGROUND Interdigestive migrating motor complexes(MMC)produce periodic contractions in the gastrointestinal tract,but the exact mechanism of action still remains *** interstitial cells of cajal(ICC-IM)participate in gastrointestinal hormone and neuromodulation,but the correlation between ICCIM and MMC is also *** found that xiangbinfang granules(XBF)mediated the phase III contraction of ***,the effects of XBF on gastric antrum motility in W/Wv mice and the effects of ICC-IM on gastric antrum MMC are *** To observe the effects of ICC-IM on gastric antrum motility and to establish the mechanism of XBF in promoting gastric antrum *** The density of c-kit-positive ICC myenteric plexus(ICC-MP)and ICC-IM in the antral muscularis of W/Wv and wild-type(WT)mice was examined by confocal *** effects of XBF on gastric antrum slow waves in W/Wv and WT mice were recorded by intracellular amplification ***-strain-gauge force transducers were implanted into the gastric antrum to monitor the MMC and the effect of XBF on gastric antrum motility in conscious W/Wv and WT *** In the gastric antrum of W/Wv mice,c-kit immunoreactivity was significantly reduced,and no ICC-IM network was *** rhythmic slow waves also appeared in the antrum of W/Wv mice,but the amplitude of the antrum slow wave decreased significantly in W/Wv mice(22.62±2.23 mV vs 2.92±0.52 mV,Pcells of the gastric antrum in WT and W/Wv mice in a dose-dependent ***,the gastric antrum motility in WT mice was significantly increased after

关键词： interstitial cells of cajal Migrating motor complex W/Wv Gastric antrum motility Xiangbinfang granules Chinese medicine

Long-pulse gastric electrical stimulation protects interstitial cells of cajal in diabetic rats via IGF-1 signaling pathway

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World Journal of Gastroenterology 2016年第23期22卷 5353-5363页

作者： Hai Li Yan Chen Shi Liu Xiao-Hua Hou Division of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology

AIM: To investigate the effects of different parameters of gastric electrical stimulation (GES) on interstitial cells of cajal (ICCs) and changes in the insulin-like growth factor 1 (IGF-1) signal pathway in streptozotocin-induced diabetic rats. METHODS: Male rats were randomized into control, diabetic (DM), diabetic with sham GES (DM + SGES), diabetic with GES1 (5.5 cpm, 100 ms, 4 mA) (DM + GES1), diabetic with GES2 (5.5 cpm, 300 ms, 4 mA) (DM + GES2) and diabetic with GES3 (5.5 cpm, 550 ms, 2 mA) (DM + GES3) groups. The expression levels of c-kit, M-SCF and IGF-1 receptors were evaluated in the gastric antrum using Western blot analysis. The distribution of ICCs was observed using immunolabeling for c-kit, while smooth muscle cells and IGF-1 receptors were identified using alpha-SMA and IGF-1R antibodies. Serum level of IGF-1 was tested using enzyme-linked immunosorbent assay. RESULTS: Gastric emptying was delayed in the DM group but improved in all GES groups, especially in the GES2 group. The expression levels of c-kit, M-SCF and IGF-1R were decreased in the DM group but increased in all GES groups. More ICCs (c-kit(+)) and smooth muscle cells (alpha-SMA(+)/IGF-1R(+)) were observed in all GES groups than in the DM group. The average level of IGF-1 in the DM group was markedly decreased, but it was up-regulated in all GES groups, especially in the GES2 group. CONCLUSION: The results suggest that long-pulse GES promotes the regeneration of ICCs. The IGF-1 signaling pathway might be involved in the mechanism underlying this process, which results in improved gastric emptying.

关键词： Long-pulse gastric electrical stimulation interstitial cells of cajal Gastric emptying IGF-1 pathway Diabetes mellitus Gastrointestinal motility disorders

Prognostic and predictive value of interstitial cells of cajal populations following stapled transanal rectal resection(STARR)in patients with obstructed defecation syndrome

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Gastroenterology Report 2018年第4期6卷 270-276,I0001,I0002页

作者： Hong-Cheng Lin Hua-Xian Chen Liang Huang Ya-Xi Zhu Qian Zhou Juan Li Yu-Jie Xu Dong-Lin Ren Jian-Ping Wang Department of Colorectal Surgery The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhou510655 GuangdongChina Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesGuangzhou510655 GuangdongChina Department of Pathology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Objective:The present study was designed to evaluate the functional outcome of stapled transanal rectal resection(STARR)and to examine the relationship between the population density of the interstitial cells of cajal(ICC)and the efficacy of the STARR operation in the management of obstructed defecation syndrome(ODS)***:Full-thickness rectal samples were obtained from 50 ODS patients who underwent *** were analysed using ICC *** and functional parameters obtained with defecography and anorectal manometry were compared with 20 ***:ICCs were significantly decreased in patients in the submucosal(SM),intramuscular(IM)andmyenteric(MY)regions when compared with the control group(P<0.05).The mean pre-operative Cleveland Constipation Score(CCS)was 24.264.1,whilst the CCS at 1,2,3,4 and 5 years post-operatively decreased significantly(P<0.05).At 3 post-operative years,58.3%(28/48)of the patients reported a favorable outcome(CCS10).On univariate analysis,the functional results were worse in those with pre-operative digitation(P=0.017),a decreased ICC-MY cell population(P=0.067),a higher resting anal canal pressure(P=0.039)and a higher rectal sensory threshold(P=0.073).Multivariate analysis showed the decreased ICC-MY cell population was an independent predictor for low unfavorable functional outcome(odds ratio=0.097,95%confidence interval:0.012–0.766).Conclusions:STARR achieved acceptable results at the cost of a slight deterioration over amore prolonged *** with a decreased ICC number in the rectal specimen showed an unfavorable functional outcome where pre-operative histological assessment of a full-thickness rectal samplemight predict for the functional outcome following STARR.

关键词： interstitial cells of cajal obstructed defecation syndrome stapled transanal rectal resection(STARR) functional outcomes

Jianpi Qingchang decoction regulates intestinal motility of dextran sulfate sodium-induced colitis through reducing autophagy of interstitial cells of cajal

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World Journal of Gastroenterology 2017年第26期23卷 4724-4734页

作者： Yan-Cheng Dai Lie Zheng Ya-Li Zhang Xuan Chen De-Liang Chen Li-Juan Wang Zhi-Peng Tang Department of Gastroenterology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Institute of Digestive Diseases Shanghai University of Traditional Chinese Medicine Experimental Teaching Center Shanghai University of Traditional Chinese Medicine

AIM To investigate the underlying effect of Jianpi Qingchang decoction(JQD) regulating intestinal motility of dextran sulfate sodium(DSS)-induced colitis in mice. METHODS C57BL/6 mice were randomly divided into four groups: the control group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except for the control group, colitis was induced in other groups by giving distilled water containing 5% DSS. Seven days after modeling, the mice were administered corresponding drugs intragastrically. The mice were sacrificed on the 15^(th) day. The disease activity index, macroscopic and histopathologic lesions, and ultrastructure of colon interstitial cells of cajal(ICC) were observed. The levels of tumor necrosis factor-alpha(TNF-α), interleukin(IL)-1β, IL-10 and interferon gamma(IFN-γ), the expression of nuclear factor-kappa B(NF-κB) p65, c-kit, microtubule-associated protein 1 light chain 3(LC3-Ⅱ) and Beclin-l m RNA, and the colonic smooth muscle tension were assessed. RESULTS Acute inflammation occurred in the mice administered DSS. Compared with the control group, the levels of IL-1β, TNF-α, IL-10 and IFN-γ, the expression of LC3-Ⅱ, Beclin-1 and NF-κB p65 m RNA, and the contractile frequency increased(P cells.

关键词： Intestinal motility interstitial cells of cajal Autophagy ulcerative colitis Jianpi Qingchang decoction