D-手性肌醇对db/db小鼠降血糖和肝脏保护作用及机制  

Effect of D-chiro-inositol on hypoglycemic and liver protection in type 2 diabetic db/db mice and its mechanism

作　　者：范春雪 魏敏 张丹丹 高庆瑶 黄菡雪 王建行[3] 韩淑英 FAN Chun-xue;WEI Min;ZHANG Dan-dan;GAO Qing-yao;HUANG Han-xue;Wang Jian-xing;HAN Shu-ying(School of Pharmacy;School of Clinical Medicine;School of Jitang;School of Basic Medical Science,North China University of Science and Technology;Hebei Key Lab on Chronic Diseases and TangshanBasic Clinical Diseases,Tangshan Hebei 063000,China)

机构地区：[1]华北理工大学药学院 [2]华北理工大学临床医学院 [3]华北理工大学冀唐学院 [4]华北理工大学基础医学院 [5]华北理工大学河北省慢性疾病重点实验室唐山市慢性病临床基础研究重点实验室,河北唐山063000

出　　处：《中国药理学通报》2018年第12期1713-1718,共6页Chinese Pharmacological Bulletin

基　　金：河北省中医药管理局科研计划项目资助课题(No2017083)

摘　　要：目的观察D-手性肌醇(DCI)对2型糖尿病db/db小鼠降血糖作用和肝损伤的抑制作用,并探究其作用机制。方法 10周龄♀db/db小鼠随机分为高剂量D-手性肌醇组(HDCI,70 mg·kg^(-1)·d^(-1))、低剂量D-手性肌醇组(LDCI,35 mg·kg^(-1)·d^(-1))和模型对照组(MCG),另设db/m为空白对照组(NCG)。灌胃给药6周,测定各组小鼠随机血糖值和给药后血糖动态变化值;给药结束时取血,测定血清AST、ALT值;HE、Masson染色和透射电镜扫描,观察DCI对db/db小鼠肝脏组织形态结构的影响;免疫组化法测定肝脏组织中葡萄糖转运蛋白4(GLUT4)的表达;Western blot法检测胰岛素受体(IR)和胰岛素受体底物2(IRS-2)的表达。结果 DCI具有降低db/db小鼠血糖的作用,能够减轻肝脏组织细胞器和细胞核的损伤,降低肝组织中脂肪变性和纤维化程度,促进GLUT4、IR和IRS-2蛋白在肝脏细胞中表达。结论 DCI具有抑制db/db小鼠肝损伤的作用,其作用机制可能是促进肝脏组织中IR,IRS2和GLUT4蛋白表达,从而减轻胰岛素抵抗,降低血糖。Aim To explore the effects of D-chiro-inositol（DCI） on hypoglycemic and liver protection in type 2 diabetic db/db mice and the underlying mechanism. Methods The type 2 diabetic db/db mice were divided into model control group （MCG）, high-dose DCI group （HDCI） and low-dose DCI group （LDCI）, and db/m mice were used as blank normal control group （NCG）. Random blood glucose levels and dynamic blood glucose after administration were measured in each group of mice. Then mouse serum of each group was taken to determine AST and ALT levels. The morphological changes of hepatic tissues were observed through HE staining, Masson staining, and transmission electron microscopy scanning. The expression of GLUT4 protein in hepatic tissues was measured by immunohistochemical method. Hepatic tissue insulin receptor （IR） and insulin receptor substrate 2 （IRS-2） were assessed by Western blot. Results DCI could reduce blood glucose in db/db mice, restrain the damage of liver cells and inhibit liver steatosis and fibrosis. Meanwhile, it could promote the expressions of GLUT4, INS and IRS-2 in liver cells. Conclusions DCI can inhibit the liver injury of db/db mice. Promoting expressions of IR, IRS2 and GLUT4 protein in liver tissues may be the mechanism of action.

关 键 词：D-手性肌醇 2型糖尿病 DB/DB小鼠 血糖 肝损伤 胰岛素抵抗 

分 类 号：R-332[医药卫生] R322.47