丹蛭降糖胶囊对2型糖尿病患者血清中TIMP-2、hs-CRP的影响及对糖尿病大鼠肾脏NF-κB的研究
本文选题:2型糖尿病 + 丹蛭降糖胶囊 ; 参考:《安徽中医药大学》2016年硕士论文
【摘要】:目的:观察具有益气养阴活血功效的中药复方丹蛭降糖胶囊(DJC)对T2DM患者血清中TIMP-2、hs-CRP的影响及对糖尿病大鼠肾脏NF-κB表达的研究,探讨炎症因子与2型糖尿病的相关性,阐述DJC对T2DM患者血管病变中炎症指标的影响,评价DJC防治和延缓糖尿病慢性并发症的作用机理。方法:1临床研究将60例2型糖尿病患者随机分为两组,每组各30例。单纯以西医综合治疗的为对照组,在西医综合治疗基础上加用丹蛭降糖胶囊(每次5粒,每日3次)的为治疗组,两组疗程均为12周。详细记录患者治疗前后FPG、Hb A1c、血脂、肌酐等指标,检测TIMP-2、hs-CRP水平。另纳入健康体检者30例作为正常组。2实验研究将55只健康雄性大鼠适应性喂养一周后,随机抽取9只作为正常对照组,余为实验组,分别予以基础饲料及高脂饲料喂养,4周后按照35mg/kg的标准予以腹腔注射链脲佐菌素(STZ),诱发出2型糖尿病大鼠模型。剔除未成模的大鼠5只,将成模的41只的大鼠随机分成4组:模型组11只,吡格列酮组、DJC高、低剂量组各10只。丹蛭高、低剂量组分别按1.08g/(kg·d)、0.54 g/(kg·d)灌胃,吡格列酮组按10mg/(kg·d)灌胃,正常对照组和模型组按5ml/(kg·d)给予生理盐水灌胃,继续给予高脂饲料喂养8周至实验结束。观察并记录各组大鼠的体重、饮水量、摄食量,检测大鼠血糖、NF-κB的阳性指数。结果:1临床研究结果临床结果显示,经丹蛭降糖胶囊治疗12周后,治疗组与对照组总有效率分别为81.5%、50%,治疗组疗效优于对照组(P0.05)。对照组与治疗组治疗后中医证候积分与同组治疗前相比均改善明显(P0.01),且治疗组治疗后中医证候积分值低于对照组治疗后中医证候积分值(P0.05)。与对照组相比,治疗组TIMP-2与hs-CRP的表达均明显下调(P0.01)。与治疗前相比,两组治疗后中医证候积分、FPG、Hb A1c、甘油三酯和总胆固醇、肌酐值、尿素氮均明显改善,差异具有统计学意义(P0.05或P0.01)。2实验研究结果动物实验结果表明,造模后,各组血糖较正常组明显升高(P0.01),治疗2周后,DJC高、低剂量组血糖明显降低(P0.01),治疗4—8周后,与模型组比较,各组血糖显著下降(P0.01)。对于大鼠肾脏NF-κB的表达,研究显示:模型组的NF-κB在肾组织中表达升高明显,特别在肾小管及肾间质细胞中最为明显,呈强阳性;在正常对照组肾组织中NF-κB基本不表达或呈弱阳性表达;DJC高、低剂量组NF-κB在肾组织中的表达降低,多为弱阳性或不表达,与模型组比较有显著性差异(P0.01);NF-κB在吡格列酮组肾组织中的表达较糖尿病模型组大鼠降低,多呈弱阳性表达。治疗后,DJC高、低剂量组中NF-κB阳性指数显著降低,与模型组比较有统计学意义(P0.01)。结论:具有益气养阴活血作用的丹蛭降糖胶囊能抑制TIMP-2、NF-κB、hs-CRP等炎症因子的强反应。其机制可能与降低血糖,减少炎症因子的高表达,调节机体免疫平衡等有关。
[Abstract]:Objective: to observe the effect of Danzhi Jiangtang capsule on the expression of TIMP-2 hs-CRP in the serum of patients with T2DM and the expression of NF- 魏 B in the kidney of diabetic rats, and to explore the correlation between inflammatory factors and type 2 diabetes mellitus. The effect of DJC on inflammatory indexes in vascular lesions of patients with T2DM was discussed, and the mechanism of DJC in preventing and delaying chronic diabetic complications was evaluated. Methods 60 patients with type 2 diabetes were randomly divided into two groups, 30 cases in each group. The control group was treated with integrated western medicine, and the treatment group was treated with Danzhi Jiangtang capsule (5 capsules per day, 3 times a day) on the basis of western comprehensive therapy. The course of treatment in both groups was 12 weeks. The serum levels of HbA1c, serum lipids, creatinine and TIMP-2 hs-CRP were recorded in detail before and after treatment. Another 30 healthy subjects were included as normal group .2 experimental study. After 55 healthy male rats were fed adaptively for one week, 9 healthy male rats were randomly selected as normal control group and the rest as experimental group. The model of type 2 diabetic rats was induced by intraperitoneal injection of streptozotocin (STZ) in accordance with the standard of 35mg/kg after feeding with basic diet and high fat diet for 4 weeks. The rats were randomly divided into 4 groups: model group (n = 11), pioglitazone group (n = 10), high DJC group (n = 10) and low dose group (n = 10). The rats in the high and low dose groups were fed with 1.08g/(kg dU 0.54 g/(kg d, the pioglitazone group 10mg/(kg d, the normal control group and the model group 5ml/(kg d respectively. The rats in the control group and the model group were fed with high fat diet for 8 weeks until the end of the experiment. The body weight, water consumption and intake of rats were observed and recorded. The positive index of NF- 魏 B was measured. Results the clinical results showed that the total effective rates of the treatment group and the control group were 81.5 and 50 respectively after treatment with Danzhi Jiangtang capsule for 12 weeks. The curative effect of the treatment group was better than that of the control group (P 0.05). The scores of TCM syndromes after treatment in control group and treatment group were significantly improved compared with those before treatment in the same group, and the integral value of TCM syndrome in treatment group was lower than that in control group after treatment (P 0.05). Compared with the control group, the expression of TIMP-2 and hs-CRP in the treatment group was significantly down-regulated (P 0.01). Compared with before treatment, the scores of TCM syndromes such as HBA1c, triglyceride, total cholesterol, creatinine and urea nitrogen were significantly improved in the two groups after treatment. The difference was statistically significant (P0.05 or P0.01.2). Compared with the normal group, the blood glucose in each group was significantly higher than that in the normal group. After 2 weeks of treatment, the level of DJC in the low dose group was higher than that in the control group. After 4-8 weeks of treatment, the blood glucose in the low dose group was significantly lower than that in the model group, and that in the low dose group was significantly lower than that in the model group. For the expression of NF- 魏 B in the kidney of rats, the expression of NF- 魏 B in the model group was significantly increased, especially in the tubules and interstitial cells. In normal control group, the expression of NF- 魏 B was almost no or weakly positive. The expression of NF- 魏 B in renal tissue of low dose group was decreased, mostly weakly positive or not. Compared with the model group, the expression of NF- 魏 B in pioglitazone group was significantly lower than that in the diabetic model group, and the expression of NF- 魏 B was weakly positive. After treatment, the positive index of NF- 魏 B in the low dose group was significantly lower than that in the model group, which was significantly higher than that in the model group (P 0.01). Conclusion: Danzhi Jiangtang capsule can inhibit the strong response of TIMP-2 NF- 魏 -hs-CRP and other inflammatory factors. The mechanism may be related to lowering blood sugar, reducing the high expression of inflammatory factors and regulating the immune balance of the body.
【学位授予单位】:安徽中医药大学
【学位级别】:硕士
【学位授予年份】:2016
【分类号】:R259
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