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参芪复方治疗糖尿病微血管病变效应机制研究

Effector Mechanisms of Shenqi Compound Recipe in Treating Diabetic Microangiopathy

【作者】 呼永河

【导师】 谢春光;

【作者基本信息】 成都中医药大学 , 中医内科学, 2013, 博士

【摘要】 目的:基于消渴六经辨证和体质分类共识,以太少二阴同病统领糖尿病微血管病变(diabetic microangiopathy, DMA)中医关键病机,观察参芪复方对糖尿病GK (Goto Kakizaki)大鼠模型肾脏、视网膜及周围神经损害效应指标的干预机制和疗效,明确DMA干预的综合作用,为参芪复方治疗DMA提供实验依据。方法:采用6个月病程的自发性糖尿病GK大鼠模型50只,随机分为5组:阴性对照组、参芪复方组、雷米普利组、导升明组、二甲双胍组,每组10只,另设SD大鼠10只为正常对照组。连续灌胃12周,以氧化酶法检测肾功能,光镜进行肾脏形态学观察,免疫组化学染色法测定NF-κB平均积分光密度值,闪光视网膜电图(flash electroretinogram, FERG)评价视网膜功能,PAS染色(periodic acid-schiff staining)测量视网膜毛细血管基底膜厚度,坐骨神经电生理测定评价周围神经传导速度。结果:参芪复方能改善GK大鼠肾功能、减轻肾脏病理损害、降低肾脏NF-κB积分光密度值,从而防治糖尿病GK大鼠肾损害;参芪复方可促进FERGa、b波振幅的恢复,缩短延迟的a、b波峰潜时,从而改善其受损的视功能,并能减轻视网膜毛细血管基底膜增厚;参芪复方可促进坐骨神经感觉神经传导速度(sensor nerve conduction velocity, SNCV)和运动神经传导速度(motor nerve conduction velocity, MNCV)的恢复,缩短其感觉神经诱发电位潜伏期(sensor-reaction latent period, SL),从而发挥防治糖尿病GK大鼠周围神经损伤的作用。结论:参芪复方可通过多途径、多靶点的系统干预,有效改善DMA模型动物肾功能、视觉功能和周围神经功能,减轻肾脏和视网膜的病理损害,从而发挥综合治疗效应,为参芪复方治疗DMA提供了一定科学实验依据。

【Abstract】 Objective: To explore the intervention mechanism and observe the effect of Shenqi Compound Recipe (SCR) in treating Goto-Kakizaki (GK) rat model of diabetes with microvascular lesions in kidney and retina, on the theortic basis of six-channel pattern identification for dispersion-thirst (xiao ke), to identify the synthesis effect of SCR in treating diabetic microangiopathy (DM), and finally, bring experimental evidence for SCR in the treatment of DM.Methods:50GK rat models with6-month disease duration were used and randomly pocessed into5groups:negative control group, SCR group, ramipril group, calcium dobesilate group and metformin group, with10rats in each group and another10normal SD (Sprague Dawley) as blank control. All the rats were intragastrically administered with SCR and control drigs for12weeks. Renal morphological observation was performed using light microscopy. Renal function was detected using oxidase test. The expression of nuclear factor kappa B (NF-κB) was detected using immunohistochemical staining method. Flash electroretinogram was used to evaluate the retinal function. Periodic acid-schiff staining was used to detect retinal capillary vascular basement membrane thickness. And sciatic nerve electrophysiology was detect to evaluate the peripheral nerve conduction velocity.Results:SCR was indicated to improve the renal function, reduce the pathologic changes in kidney, decrease the expression of NF-κB in GK rats, thus protect GK rats from renal damages. Experiments showed that SCR played a role in rehabilitating the amplitude both of a and b waves in flash electroretinogram, and shortening the peak latency both of a and b waves, thus improving the damaged visual function and reducing retinal capillary vascular basement membrane thickness. SCR was also indicated to restore both sensory nerve conduction velocity as well as motor nerve conduction velocity of sciatic nerve, and shorten the sensor-reaction latent period, protect diabetic GK rats from peripheral nerve injury.Conclusion:SCR can significantly improve the renal function, visual function and peripheral nerve function of diabetic GK rats via multiple treatment targets and multiple ways, to reduce the pathological damages both in kidney and retina, thus playing a comprehensive role in the treatment of DM.

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