摘要
目的:研究罗格列酮(RSG)给药不同时间对2型糖尿病模型小鼠肾组织中膜结合型前列腺素E2合酶-1/前列腺素E2(m PGES-1/PGE2)水平的影响。方法:将小鼠随机均分为正常对照组、模型组、RSG 1周组、RSG 4周组、RSG 8周组和RSG 12周组,每组6只,后5组小鼠分别建立2型糖尿病模型。RSG各组小鼠腹腔注射RSG 4 mg/(kg·d),分别连续给药1、4、8、12周,末次给药后分别收集每只小鼠24 h尿液,检测其24 h尿量及尿液中PGE2、前列腺素D2(PGD2)、血栓素B2(TXB2)水平;再检测肾组织中环氧合酶(COX)-1、COX-2、m PGES-1、m PGES-2、15-羟基前列腺素脱氢酶(15-PGDH)、过氧化物酶体增殖物激活受体γ(PPAR-γ)蛋白水平及前列腺素E2受体1(EP1)及EP4m RNA水平。结果:与正常对照组比较,模型组小鼠24 h尿量明显增多,且尿液中PGE2、PGD2、TXB2水平明显升高(P<0.05),经RSG治疗后能以时间依赖性方式降低PGE2水平。糖尿病模型组小鼠较正常对照组小鼠肾组织中m PGES-1、COX-2、PPAR-γ蛋白水平明显升高(P<0.05),而m PGES-2、COX-1、15-PGDH和EP1、EP4m RNA水平未见明显改变。给予RSG治疗后能使模型小鼠的PPAR-γ、m PGES-1水平呈阶梯式降低,与给药时间呈正相关,但差异无统计学意义;EP4m RNA水平明显降低(P<0.05)。结论:RSG有望通过下调m PGES-1/PGE2/EP4表达水平来改善2型糖尿病肾脏病变。
OBJECTIVE: To study the effects of different administration time of rosiglitazone (RSG) on the level of mPGES-1/ PGE2 in renal tissue of type 2 diabetic model mice. METHODS: Mice were randomly assigned into normal control group, model group, RSG 1 week group, RSG 4 week group, RSG 8 week group and RSG 12 week group with 6 mice in each group. The type 2 diabetic model were established in the latter 5 groups, and RSG groups were given RSG 4 mg/(kg·d) intragastrically for 1, 4, 8 and 12 weeks, respectively. After last administration, 24 h urine were collected, and 24 h urine volume and the levels of PGE2, PGD2 and TXB2 in urine were detected. The protein levels of COX-1, COX-2, mPGES-1, mPGES-2, 15-PGDH and PPAR-7 and mRNA levels of EP1 and EP4 were detected in renal tissue. RESULTS: Compared with normal control group, 24 h urine and the levels of PGE2, PGD2 and TXB2 were increased significantly in model group (P〈0.05) ; the level of PGE2 was decreased in time-dependent manner after RSG treatment. Compared with normal control group, the protein level of mPGES-1, COX-2 and PPAR-γ in renal tissue were increased significantly in diabetic model group (P〈0.05), while the levels of mPGES-2, COX-1, 15-PGDH and mRNA levels of EP1 and EP4 had no significant change. After RSG treatment, the protein level of PPAR-7 and mPG- ES-1 were stepped down, which was associated with administration time positively, there was no statistical significance, mRNA level of EP4 was decreased significantly (P〈0.05). CONCLUSIONS: RSG can improve type 2 diabetes renal lesions through downregulating the expression of mPGES-1/PGEJEP4.
出处
《中国药房》
CAS
CSCD
2014年第45期4248-4251,共4页
China Pharmacy
基金
泉州市科技计划立项项目(No.2014Z38)