双醋瑞因对2型糖尿病大鼠炎性因子和脂代谢的影响及脂肪组织chemerin的表达变化
Effects of diacerein on inflammatory cytokines and adipose metabolism as well as the expression of chemerin in adipose tissue of type 2 diabetic rats

摘要：目的 探讨双醋瑞因及其代谢产物大黄酸对2型糖尿病(T2DM)大鼠血清炎症因子和肾周脂肪组织chemerin蛋白表达水平的影响及调节糖脂代谢的作用。方法 56只雄性SD大鼠随机分组，正常对照组(A组)予普通饲料，其余各组予高脂饲料喂养；第8周末，经腹腔注射链脲佐菌素(STZ)溶液造模(A组予注射同等体积无菌柠檬酸钠溶液)，于第10周末根据OGTT实验结果筛选成模大鼠，分别分为T2DM组(B组)、吡格列酮组(C组)、双醋瑞因组(D组)、吡格列酮+双醋瑞因组(E组)，干预4周。实验第10、14周末禁食不禁水取血并检测血糖、血脂、空腹胰岛素(FINS)、白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)。第14周末心脏取血后，处死所有大鼠并分离大鼠肾周脂肪组织，Western blotting检测肾周脂肪组织chemerin表达。结果 第10周末，B、C、D、E组的空腹血糖(FBG)、FINS、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、IL-1β、IL-6、TNF-α均高于A组(P<0.01)，高密度脂蛋白胆固醇(HDL-C)低于A组(P<0.01)。第14周末，C、D、E组FBG、FINS、TC、TG、LDL-C、IL-1β、IL-6、TNF-α均低于B组而高于A组(P<0.05)，而HDL-C低于A组(P<0.05)。E组糖脂代谢及炎症因子水平变化大于C、D组(P<0.05)。Western blotting结果显示，B组chemerin表达增高，高于其他组(P<0.05)，而C、D组chemerin表达高于A、E组(P<0.05)，A组与E组差异无统计学意义。结论 双醋瑞因可能通过影响糖尿病大鼠chemerin及相关炎症细胞因子表达，调节血脂代谢，改善胰岛素抵抗，遏制T2DM发展。
ABSTRACT: Objective To study the effects of diacerein and its metabolite rhein on plasma inflammatory cytokine level and expression of perirenal adipose tissue chemerin in type 2 diabetes mellitus (T2DM) rats and its role in regulating glucose and lipid metabolism. Methods We randomly divided 56 SD male rats into 5 groups: normal control group (Group A), T2DM group (Group B), pioglitazone group (Group C), diacerein group (Group D), and pioglitazone+diacerein group (Group E). Group A was fed with ordinary feed whereas the other groups were fed with high-fat diet. At the end of week 8, rats in Groups B, C, D and E were injected intraperitoneally with 30mg/kg of STZ solution to create the model. Those in Group A were injected with the same volume of sterile sodium citrate solution. OGTT examination was taken to screen the model rats at the end of week 10. The successful mode was chosen according to OGTT result. Then Group C was treated with pioglitazone 10mg/(kg？d) orally, Group D with diacerein 50mg/(kg？d), Group E with pioglitazone 10mg/(kg？d)+diacerein 50mg/(kg？d), and Group A and B were given the same volume of normal saline. The intervention lasted 4 weeks. At the end of experiment weeks 10 and 14, FBG, FINS, TC, TG, LDL-C, IL-1β, IL-6, and TNF-α were detected in the fasting rats with free access to water. After blood sample was taken at the end of week 14, all rats were killed and the perirenal adipose tissue was isolated, the expression of chemerin in perirenal adipose tissue was detected by Western blotting. Results At the end of week 10, FBG, FINS, TG, TC, LDL-C, IL-1β, IL-6, and TNF-α were higher in Groups B, C, D and E than in Group A while HDL-C was lower (all P<0.01). At the end of week 14, TC, TG, and LDL-C were lower in Groups C, D and E