文章摘要
段玉敏,袁振芳.肥胖 2型糖尿病模型 OLETF大鼠不同病程阶段肝脏水通道蛋白 9 mRNA的表达[J].安徽医药,2021,25(5):1003-1006.
肥胖 2型糖尿病模型 OLETF大鼠不同病程阶段肝脏水通道蛋白 9 mRNA的表达
Expression of hepatic aquaporin 9 mRNA in OLETF rats with obesity type 2 diabetes melli? tus at different stages
  
DOI:10.3969/j.issn.1009-6469.2021.05.039
中文关键词: 水通道蛋白 9  糖尿病, 2型  肥胖  大鼠,近交 OLETF
英文关键词: Aquaporin 9  Diabetes mellitus, type 2  Obesity  Rats, inbred OLETF
基金项目:
作者单位
段玉敏 北京市第六医院内分泌科北京100007 
袁振芳 北京大学第一医院内分泌科北京 100034 
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中文摘要:
      目的观察肥胖 2型糖尿病模型 OLETF大鼠在不同糖尿病病程阶段肝脏组织水通道蛋白 9(AQP 9)mRNA表达的变化,探讨 AQP 9在肥胖及糖尿病发病中的作用。方法取 OLETF大鼠 30只为实验组,同种系的非糖尿病 LETO大鼠 18只为正常对照组。 8周(基线)时两组大鼠分别处死 6只。然后将 OLETF大鼠分为未治疗组( OLETF组) 12只及盐酸二甲双胍治疗组(OLETF/M组) 12只。分别观察每组大鼠在 8周、 18周、 28周时的体质量、血清三酰甘油、胆固醇,行葡萄糖耐量试验测定血糖与胰岛素水平,用 Real-time PCR测定肝脏组织 AQP9 mRNA的表达。结果 OLETF组在 18周均患糖尿病, 28周的血糖水平与 18周大致相当,随周龄增加其体质量、血糖、胰岛素、血清三酰甘油、胆固醇均明显增高。肝脏组织 AQP 9 mRNA表达在 8周、 18周及 28周龄分别是同周龄 LETO组的 0.9倍, 1.0倍及 0.7倍。 OLETF/M组在 18周均患糖尿病,但血糖水平低于 OLETF组; 28周血糖均恢复为糖耐量异常。 OLETF/M组的体质量、胰岛素水平与 OLETF组差异无统计学意义,三酰甘油、胆固醇水平较 OLETF组低。肝脏组织 AQP 9 mRNA表达在 8周、 18周及 28周龄分别是同周龄 LETO组的 0.9倍, 0.6倍及 0.5倍。结论 OLETF大鼠随周龄增加,肥胖、高脂血症、胰岛素抵抗加重,血糖增高。 OLETF组和 OLETF/M组的肝脏组织的 AQP 9 mRNA表达均呈先上调后下调的趋势,提示脂肪分解先增强后减弱。 OLETF/M组肝脏组织 AQP 9的 mRNA表达水平均较同周龄 OLETF组低。盐酸二甲双胍可以改善 OLETF/M组大鼠的糖脂代谢紊乱并抑制肝脏 AQP 9 mRNA的表达。肝脏 AQP 9在肥胖和糖尿病的病程中起一定的作用。
英文摘要:
      Objective To observe the changes of aquaporin 9 (AQP9) mRNA expression in liver in the spontaneous type 2 diabetesanimal model OLETF (Otsuka Long-Evans Tokushima Fatty) rats at different stages and to explore the role of AQP9 in obesity development and diabetes.Methods OLETF rats (n=30) were studied, with same strains of non-diabetic Long-Evans Tokushima Otsuka (LETO) rats (n=18) used as age-matched normal controls. At 8 weeks (baseline), 6 rats in each of the two groups were sacrificed. ThenOLETF rats were divided into no treatment group (OLETF group, n=12) and metformin hydrochloride treatment group (OLETF/Mgroup, n=12). At the age of 8 weeks, 18 weeks and 28 weeks, body weights were obtained, biochemical items were measured, includingserum triglyceride, cholesterol, glucose, insulin level with oral glucose tolerance test (OGTT). Liver were obtained for the measurementof AQP9 mRNA expression by real-time PCR.Results 1. Rats in OLETF group developed diabetes at 18 weeks, the glucose were almost same level at 28 weeks with 18 weeks. Body weight and biochemical items including glucose and insulin of OGTT, serum triglyceride, serum cholesterol, were increased with rats′ age. At the age of 8 weeks, 18 weeks and 28 weeks, liver AQP9 mRNA expression inOLETF group were decreased 0.9 times, 1.0 times and 0.7 times. 2. Rats OLETF/M group developed diabetes at 18 weeks, but the glucose level was lower than that of age-matched OLETF group rats. At 28 weeks, the rats′ glucose improved, rats returned to impaired glucose tolerance. The body weight and insulin of OGTT of OLETF/M group rats were of no significant difference with those of the OLETFgroup rats. Biochemical items including serum triglyceride, serum cholesterol were lower than those of the OLETF groups rats. At theage of 8 weeks, 18 weeks and 28 weeks, liver AQP9 mRNA expression in the OLETF/M group were decreased 0.9 times, 0.6 times and 0.5 times.Conclusion The degrees of obesity, dyslipidemia, insulin resistance and glucose of OLETF rats are significantly increasedwith rats′ age. LiverAQP9 mRNA expression are increased at week 18 but decreased at week 28, which means lipolysis is increasedearlier then decreased. The expression of AQP9 in liver in OLETF/M group is lower than that in the age-matched OLETF group. Metformin hydrochloride can improve the OLETF/M rats′ lipid metabolism and glucose metabolism disorders. It also can inhibit the expression of AQP9 in liver. Liver AQP9 may play an important role in the development of obesity and diabetes.
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