辛伐他汀改善肥胖合并骨质疏松雌性大鼠肝脏损伤的作用及机制  

Research on improvement and mechanisms of simvastatin in liver damages of obese and osteoporotic female rats

作　　者：陈勇[1] 李朝飞 朱致祥 朱小欢[2] 代芳[2] 张楠[2] 章秋[2] 鲁云霞[1] CHEN Yong;LI Chao-fei;ZHU Zhi-xiang;ZHU Xiao -huan;DAI Fang;ZHANG Nan;ZHANG Qiu;LU Yun- xia(Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei 230032, Anhui, Chin)

机构地区：[1]安徽医科大学基础医学院,安徽合肥230032 [2]安徽医科大学附属第一医院内分泌科,安徽合肥230022

出　　处：《广东医学》2018年第11期1629-1634,共6页Guangdong Medical Journal

基　　金：国家中医临床研究基地业务建设科研专项课题(编号:JDZX2015129);安徽省自然科学基金项目(编号:1608085MH208);安徽省青年科学基金项目(编号:1608085QH205)

摘　　要：目的观察辛伐他汀干预对肥胖合并骨质疏松雌性大鼠肝脏损伤的作用,并探讨其可能的机制。方法 40只雌性SD大鼠随机分为假手术对照组(SHAM组)、去卵巢组(OVX组)、去卵巢+高脂组(OVX+HFD组)、去卵巢+高脂+辛伐他汀治疗组(OVX+HFD+SIM组),高脂饲料和辛伐他汀[10 mg/(kg·d)]灌胃分别为16周和8周,葡萄糖和胰岛素耐量试验分析大鼠的胰岛素抵抗情况,检测血脂指标,HE染色观察肝脏的病理学变化,RT-PCR、免疫组化和Western blot分析内质网应激分子ATF6、GRP78、CHOP、NF-κB、CD68、TLR4的表达。结果与SHAM组相比,OVX组和OVX+HFD组大鼠血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平显著升高(P<0.05),高密度脂蛋白胆固醇(HDL-C)水平明显降低(P<0.05),肝细胞出现水肿变性,TLR4、NF-κB、CD68、GRP78、CHOP的表达显著升高,以OVX+HFD组变化更为明显。与OVX+HFD组相比,OVX+HFD+SIM组大鼠血清TG、TC、LDL-C降低,HDL-C升高,肝细胞的水肿变性明显减少,TLR4及CD68、GRP78、CHOP的表达显著降低。结论辛伐他汀具有显著的降脂和改善胰岛素抵抗的作用,可能是通过减轻肝细胞中内质网应激、炎性细胞浸润来实现的。Objective To observe the effect of simvastatin treatment on liver damage in obese female SD rats merged with osteoporosis and probe into possible mechanisms. Methods Forty female SD rats were randomly divided in- to sham operated group （Group Sham）, ovariectomized group （Group OVX）, ovariectomized group treated with high -fat diet （ Group OVX ＋ HFD） and OVX ＋ HFD treated with simvastatin group （ Group OVX ＋ HFD ＋ SIM）. Glucose toler- ance test （GTT） and insulin tolerance test （ITT） were used to examine changes of insulin sensitivity. Serum biochemical indices were detected. HE staining was used to observe the pathological changes in liver tissues. Expression of CD68, TLR4, NFKB, glucose regulated protein 78 （GRP78） and GADD153 （CHOP） were analyzed by immunohistochemistry, RT - PCR and western blot, respectively. Results Compared with Group SHAM, serum TG, TC and LDL - C levels were significantly higher, while HDL - C level was markedly lower, the structure showed obvious edema and degeneration in liver cells were observed in Group OVX ＋ HFD and Group OVX. Expression of TLR4, CD68, NFKB, GRP78 and CHOP were significantly increased in Group OVX ＋ HFD and Group OVX, the changes were more obvious in Group OVX ＋ HFD. Compared with Group OVX ＋ HFD, serum TG, TC and LDL - C levels were reduced and HDL - C level was increased, while edema and degeneration in liver cells were significantly reduced in Group OVX ＋ HFD ＋ SIM, while expression of TLR4, CD68, NFKB, GRP78 and CHOP were obviously reduced in liver tissue. Conclusion Simvastatin has hypolipi- demic effect and alleviate IR, which maybe mediated by the reduction of ERS and inflammatory infiltration in liver tissues.

关 键 词：辛伐他汀 肥胖 骨质疏松 肝脏 损伤 

分 类 号：R580[医药卫生—内分泌] R589.2[医药卫生—内科学]