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Acta Pharmacologica sinica 2004年第4期25卷 64-70页

作者： Yue-juan QIN1, Zhen-lin ZHANG, Qi-ren HUANG, Jin-wei HE, Yun-qiu HU, Qi ZHOU, Jing-hui LU, Miao LI, Yu-juan LIU center for preventing and treating osteoporosis, osteoporosis research unit, {2. jiaotong universityaffiliated sixth people’s hospital, shanghai 2.02.3, china center for preventing and treating osteoporosis Osteoporosis Research Unit Shanghai JiaoTong University Affiliated Sixth People\'s Hospital Shanghai 200233 China

AIM: To investigate if vitamin D receptor (VDR) gene Apa I polymorphism and estrogen receptor-α (ER-α) gene Pvu II, Xba I polymorphisms are related to bone mineral density (BMD), bone mineral content (BMC) and bone size in premenopausal Chinese women. METHODs: The VDR Apa I genotype and ER-α Pvu II, Xba I genotype were determined by PCR-restriction fragment length polymorphism (RFLP) in 493 unrelated healthy women aged 2.-40 years of Han nationality in shanghai city. BMD (g/cm2., BMC (g), and bone areal size (BAs, cm2. at lumbar spine 1-4 (L1-4) and proximal femur (femoral neck, trochanter and Ward’s triangle) were measured by duel-energy X-ray absorptionmetry. REsULTs: All allele frequencies did not deviate from Hardy-Weinberg equilibrium. After pheno- types were adjusted for age, height, and weight, a significant association was found between VDR Apa I genotype and BMC variation at L1-4and Ward’s triangle (Ps at lumbar spine and proximal femur. ER-α Pvu II, Xba I genotype was not related to BMC, BMD, and BAs at all sites. CONCLUsION: The study suggested that Apa I polymorphism in VDR gene may influence on attainment and maintenance of peak bone mass in premenopausal Chinese women.

关键词： bone density bone remodeling calcitriol receptors estrogen receptors restriction fragment length polymorphism gene frequency genotype female

Direct transfer of A2. gene into pancreas protected mice from streptozotocin-induced diabetes

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Acta Pharmacologica sinica 2004年第6期25卷 19-24页

作者： Lu-yang YU, Bo LIN, Zhen-lin ZHANG2. Li-he GUO3 Instituteof Biochemistryand Cell Biology, shanghai Institutes for Biological sciences, Chinese Academy ofsciences, shanghai 2.0031 {2., osteoporosis research unit, 2. shanghai jiaotong universityaffiliated sixth people’s hospital, shanghai 2.02.3, china Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences center for preventing and treating osteoporosis Osteoporosis Research Unit Shanghai JiaoTong University Affiliated Sixth People’s Hospi

AIM: To investigate the efficiency of transfer of A2. gene into pancreas against sTZ-induced diabetes. METHODs: PVP-plasmid mixture was directly transferred into the pancreatic parenchyma 2. d before sTZ injection. The uptake of plasmid pcDNA3-LacZ or pcDNA3-A2. was detected by PCR and the expression of LacZ was confirmed by histological analysis with X-gal. A2. expression in the pancreas of pcDNA3-A2. transgenic mice was measured by RT-PCR and Western blots. Urine amylase, NO generation, and histological examination were examined. REsULTs: Injection of PVP-plasmid mixture directly into the pancreatic parenchyma increased urine amylase concentration 16 h after operation and reversed it to nearly normal 36 h later. On d 33 LacZ expression could be found in spleen, duodenum, and islets. The development of diabetes was prevented by direct A2. gene transferring into the pancreas and A2.-mediated protection was correlated with suppression of NO production. The insulitis was ameliorated in A2.-treated mice. CONCLUsION: Injection of PVP-plasmid mixture directly into the pancreatic parenchyma led to target gene expression in islets. Direct transfer of A2. gene into the pancreas protected mice from sTZ-induced diabetes.

关键词： adenoviridae streptozocin insulin-dependent diabetes mellitus gene therapy nitric oxide glucose amylases reversed transcriptase polymerase chain reaction Western blotting

CMV-hFasL transgenic mice are sensitive to low doses of streptozotocin-induced type Ⅰ diabetes mellitus

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Acta Pharmacologica sinica 2003年第12期 25-30页

作者： LIN Bo, ZHANG Zhen-Lin~2. YU Lu-Yang, GUO Li-He~3 Institute of Biochemistry and Cell Biology, shanghai lnstitute for Biological sciences, Chinese Academy of sciences shanghai 2.0031 ~2.2., osteoporosis research unit, shanghai jiaotong University Affiliated sixth people's hospital, shanghai 2.02.3, china

AIM: To investigate the role of Fas-FasL pathway in the pathogenesis of streptozotocin (sTZ)-induced type Ⅰ diabetes mellitus. METHODs: Low dose injections of sTZ were used to induce type Ⅰ diabetes mellitus in the CMV-hFasL transgenic mice. Blood glucose concentration was measured with Glucotrand Plus blood glucose test strips. Expression of hFasL was detected by RT-PCR and Western blotting. The severity of insulitis was determined by histological examination. Expressions of IL-1β and TNF-α mRNA in the pancreas were detected by semi-quantitative RT-PCR analysis. Fas expression in apoptotic RIN-5F cells was also confirmed by RT-PCR in vitro. REsULTs: hFasL was expressed in the islets of CMV-hFasL transgenic mice. The transgenic mice were sensitive to diabetic induction than the control WT mice. IL-1β and TNF-α expressions in the pancreas of CMV-hFasL transgenic mice were far more than that in WT mice. We also found sTZ and IL-1β could both induce higher expression of Fas in RIN-5F. The combining

关键词： transgenic mice Fas Fas ligand type Ⅰ diabetes mellitus streptozotocin apoptosis interleukin-1 tumor necrosis factor

Association of polymorphisms in low-density lipoprotein receptor-related protein 5 gene with bone mineral density in postmenopausal Chinese women

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Acta Pharmacologica sinica 2005年第9期26卷 1111-1116页

作者： Zhen-lin ZHANG~2.Yue-juan QIN Jin-wei HE Qi-ren HUANG Miao LI Yun-qiu HU Yu-juan LIU center for preventing and treating osteoporosis,osteoporosis {2. unit,the sixth people’s hospital,shanghai jiaotong University,shanghai 2.02.3,china centerforpreventingand{2.osteoporosis OsteoporosisResearchUnittheSixthPeople'sHospitalShanghaiJiaotong

Aim:To investigate the possible association of Q89R,N740N and A1330V poly-morphisms in low-density lipoprotein receptor-related protein 5(LRP5)gene withbone mineral density(BMD)in postmenopausal Chinese ***:Q89R,N740N and A1330V genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)in 647 unrelated healthypostmenopausal Han Chinese women aged 43-76 years in *** atlumbar spine 1-4 and the left proximal femur including the femoral neck,trochanterand Ward’s triangle were measured by dual-energy X-ray absorptionmetry in ***:The distribution of the Q89R,N740N and A1330V genotypesin this population was as follows:QQ 80.5%,QR 18.7%,and RR 0.8%;TT 66.9%,TC 31.1%,and CC 2.0%;AA 68.0%,AV 2..7%,and VV 2.3%.The frequencies of theQ89R,N740N and A 1330V genotypes and alleles did not deviate from the Hardy-Weinberg *** found that the Q89R and A1330V polymorphisms werein linkage disequilibrium in our population(x~2.13.50,Psting for age,years since menopause,height,and weight,the Q89R or N740Ngenotypes were significantly associated with BMD at the femoral neck(Psubjects with the Q89R QQ genotype or the N740N TT genotype had a signifi-cantly higher BMD at the femoral neck,compared with those with the QR/RR orTC/CC genotypes,*** significant association was found betweenA1330V polymorphism and BMD at any ***:Our findings suggestthat the LRP5 gene is a candidate for the genetic determination of BMD in post-menopausal Chinese women.

关键词： bone density low-density lipoprotein receptor-related protein 5 polymorphism

EFFECTs OF LEVOTHYROXINE ON BONE METABOLIsM IN PATIENTs WITH DIFFERENTIATED THYROID CANCER AFTER OPERATION AND ^(131)I ABLATION

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Journal of shanghai second Medical University(Foreign Language Edition) 2007年第2期19卷 95-99页

作者：陈立波罗全勇余永利袁志斌陆汉魁朱瑞森章振林 Department of Nuclear Medicine the Sixth People's Hospital Shanghai Jiaotong University Prevention and Treatment center of osteoporosis the Sixth People's Hospital Shanghai Jiaotong University

Objective To investigate the effects of substitutive and suppressive doses of levothyroxine on bone metabolism in patients with differentiated thyroid carcinoma after surgery and 131I ablation. Methods The patients, who had received levothyroxine(L-T4) for at least 3 years for treating their differentiated thyroid carcinoma after surgery and 131I therapy, were classified into substitutive group and suppressive group according to the levels of serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TsH). We compared the levels of FT3, FT4, TsH, serum parathyroid hormone (PTH), serum calcium (Ca), serum phosphate (P), serum alkaline phosphates (ALP) and Bone mineral density (BMD) to those of healthy volunteers well matched for sex, age, menopausal status, and body mass index (BMI). Results No significant differences were found in the bone density and biochemical parameters of bone metabolism of the subjects treated with substitutive or suppressive doses of L-T4 compared with the control subgroup. No significant differences were observed among the subgroups according to accumulative doses of 131I. No bone fracture was found in all the patients. Conclusion The substitutive and suppressive doses of L-T4 are safe and necessary for patients with differentiated thyroid carcinoma after surgery and 131I therapy. such treatment for 3 years is not associated with increased risk of osteoporosis. Much longer term of follow up is still needed in patients receiving substitutive and suppressive doses of L-T4.

关键词： subclinical hyperthyroidism differentiated thyroid carcinoma bone metabolism levothyroxine ^131I

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