【作者】 苏晓燕；

【导师】 邢学农；

【作者基本信息】 安徽医科大学 ， 内科学， 2008， 硕士

【摘要】 目的近年研究发现他汀类药物除调脂作用外,对骨代谢亦有影响。以往一些研究以观察他汀类药物促进骨形成为主,该药是否抑制骨吸收报道极少。本实验设计了糖尿病大鼠应用辛伐他汀的实验性研究以观察该药是否可以通过抑制骨吸收而阻止糖尿病大鼠骨质疏松的发生及发展,并探讨其可能的机制,进而为糖尿病合并骨质疏松的防治提供实验依据。方法健康雄性Wistar大鼠24只(安徽医学研究所实验动物中心提供),2月龄,体重200±20克,实验前测鼠尾血糖均正常,随机分为三组:A组,正常对照组;B组,糖尿病对照组;C组,辛伐他汀治疗组,每组各8只。糖尿病模型建立成功后,C组每日以辛伐他汀20mg/kg.d(默沙东中国有限公司),溶于蒸馏水中灌胃给药,A,B组喂以等量生理盐水。检测各组第2,4,8周血糖,于第2周、第8周以代谢笼收集12小时尿液,准确计量,混匀后留取5ml,用酶联免疫法测尿I型胶原氨基端肽,第8周末处死大鼠经股动脉取血,用酶联免疫法测血I型胶原氨基端肽,骨密度仪测全身骨密度。后仔细剔除大鼠双下肢股骨周围肌肉组织,测定双侧股骨骨密度,并留取三组大鼠的股骨骨标本光镜观察镜下改变。结果(1)各组间血糖比较:2,8周时B,C组均显著高于A组(P<0.01),B,C组组间无统计学差异(P>0.05)。(2)各组间尿NTX比较:第2周末B组、C组显著高于A组(P<0.01);第8周末与第2周末组内比较B组尿NTX有上升,而C组经辛伐他汀治疗后NTX较治疗前有明显下降,差异有统计学意义(P<0.05),但仍然高于A组。(3)各组间血NTX比较: B组、C组显著高于A组(P<0.01),C组经辛伐他汀治疗后较B组有明显下降。(4)各组间骨密度比较: B,C组较正常对照组明显低减, C组经辛伐他汀治疗后骨密度较B组高,差异有统计学意义P<0.05,但与A组相比,仍有较大差距,差异有统计学意义(P<0.01)。(5)各组光镜下骨组织病理变化与A组比较,B组光镜下所见(1:400)骨小梁明显变细、稀疏、断裂,其间较多脂肪组织。C组投食辛伐他汀后骨质疏松病理改变有所改善,但与A组相比,仍有明显骨质疏松表现。结论:辛伐他汀对糖尿病大鼠骨组织有明确的保护作用,其作用机制可能与抑制骨吸收有一定关系,确切的机制值得进一步深入研究。更多还原

【Abstract】 Objective: Some recent researches have show that statins have some influence on bone metabolism besides its fat adjustment. Most researches paid close attention mainly about its promotion to bone formation, and few reports showed that statins can restrains bone absorption. This experiment was designed to observe if simvastatin can hold back the development and progression of osteoporosis through restraining bone absorption, then we can provide experimental base for the prevention and treatment of osteoporosis related to diabetes mellitusMethod :24 healthy male Wistar rats (provided by Experimental Animal Centre of Anhui Medical Graduate School, two months old, 200±20g weight, with blood glucose up to snuff before experiment) were randomly assigned t three groups. normal control group (groupA,n=8), diabetic rats group( groupB,n=8) and simvastatin(20mg/kg/d) treatment group (group C, n =8). After diabetic models were estabished, group C were given simvastatin (MERCK China C.Ld) 20mg/kg each day ( with simvastatin dissolved in distilled water). Group A and Group B were given equal distilled water. The peripheral blood glucose at the 2nd , 4th , 8th week, and N-terminal telopeptide of type I Collagen (NTX) at 2nd and 8th week(24 hours urine) were measured with enzyme-linked immunosorbent assay( ELISA). By the 8th week, rats were killed to collect blood and bone specimen, the blood NTX was measured by ELISA, the bone mineral density(BMD) of lower limbs was measured by Dual Energy X-ray Absorptiometry(DXA), Bone specimen of lower limbs from rats of each group were kept to observe their morphology under light microscope.Results:(1)The peripheral blood glucoses of group B and group C at the 2nd and 8th week of were markedly higher than that of Group A(P<0.01), there was no statistical difference between Group B and group C(P>0.05). (2)The 12 urine NTX in group B and group C by the end of 2nd week was markedly higher than that of group A(P<0.01), the urine NTX of the 8th week of group B was higher than that of the 2nd week. The urinary NTX of group C declined markedly after statins treatment, and the difference has statistical meanings(P<0.05), but still higher than that of the group A. (3)The blood NTX of group B and group C was markedly higher than that group A(P<0.01), but the level in group C declined greatly when compared with that of group B after treatment with statins. (4)The BMD of group B and group C declined markedly compared with group A; The BMD of group C was higher than that of group B after the treatment with statins, and the difference had statistical signficant(P<0.05), but still lower much than that of group A, and the difference had statistical significance, too(P<0.01). (5)Compared with group A, the bone trabecula of group B markedly turned thin, sparseness and rupturable under light microscope(1:400) with much adipose tissue. the bone trabecula in group C had became better in osteoporosis after treatment with simvastatin for 8weeks, but still had distinct osteoporosis characteristic under light microscope.Conclusion: Simvastatin has some protective effect against osteoporosis in STZ-induced diabetes rats , which may be partly related to its effect in inhibting bone absorption, exact mechanisms need to be evaluated futher.更多还原