维格列汀调控PKC-η及PKC-ζ表达以改善2型糖尿病大鼠肾功能的研究

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目的:分析维格列汀干预2型糖尿病大鼠后,大鼠肾脏病理学、肾功能、血脂、PKC-η以及PKC-ζ治疗前后的变化特点。方法:将60只雄性SD大鼠随机分为空白组(control group,CG)、高脂饮食组(high fat group,HFG)以及维格列汀治疗组(vildagliptin group,VG),每组20只。HFG、VG给予高脂高糖饮食6个月建立2型糖尿病大鼠模型,模型建立成功后VG给予维格列汀57 mg·kg-1·d-1灌胃治疗,HFG给予相应生理盐水灌胃,CG不给予任何干预。分别在治疗4周和8周后处死大鼠各半,收集血清及肾脏行相关指标学检测。结果:大鼠肾脏切片HE染色可见,CG清晰无损伤;HFD在有一定的炎症反应,属于肾脏损害初期;治疗4周后VG即有明显变化,治疗8周后VG与CG基本一致。VG与HFG相比,治疗4周后血尿素、血肌酐、血尿酸、血尿素氮、总胆固醇、甘油三酯、低密度脂蛋白胆固醇明显降低(P<0.05),治疗8周后数值基本与治疗4周后一致,HDL-C治疗后没有改变;治疗4周后肾脏中PKC-η以及PKC-ζmRNA和蛋白表达明显降低(P<0.05),治疗8周后进一步降低,但变化不明显。结论:维格列汀可调节大鼠血脂,进而改善2型糖尿病大鼠肾功能,这可能与其降低肾脏中PKC-η以及PKC-ζ表达有关。 OBJECTIVE: To analyze the changes of vildagliptin in diabetic rats before and after treatment of renal pathology, renal function, blood lipids, PKC-η and PKC-ζ. Methods: Sixty male Sprague Dawley rats were randomly divided into control group (CG), high fat group (HFG) and vildagliptin group (VG) . HFG and VG were given high fat and high glucose diet for 6 months to establish type 2 diabetic rat model. VG was given to Vogliptin 57 mg · kg-1 · d-1 by intragastric administration and HFG was given saline Stomach, CG do not give any intervention. The rats were sacrificed at 4 and 8 weeks after treatment, respectively, and serum and kidneys were collected for relevant index tests. Results: The kidneys of rats were stained with HE and the CG was clear and non-destructive. HFD had a certain inflammatory reaction, which belonged to the early stage of renal damage. The VG had obvious changes after 4 weeks of treatment, and VG and CG were basically the same after 8 weeks of treatment. Compared with HFG, blood urea nitrogen, serum creatinine, blood uric acid, blood urea nitrogen, total cholesterol, triglyceride and low density lipoprotein cholesterol were significantly decreased after 4 weeks of treatment (P <0.05). After 8 weeks of treatment, After 4 weeks of treatment, there was no change after HDL-C treatment. The expression of PKC-η and PKC-ζmRNA and protein in the kidney were significantly decreased after 4 weeks of treatment (P <0.05), and further decreased after 8 weeks of treatment, but the changes were insignificant. CONCLUSION: Vildagliptin can regulate the blood lipids in rats and further improve renal function in type 2 diabetic rats, which may be related to the decrease of PKC-η and PKC-ζ expression in the kidney.
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