益气养阴活血法对糖尿病患者血清CTRP-9、Hcy的干预及对糖尿病大鼠CXCL-5、TNF-α的影响

发布时间：2018-10-09 09:50

【摘要】：目的:观察具有益气养阴活血功效的丹蛭降糖胶囊(DJC)对2型糖尿病(T2DM)血管病变补体C1q/肿瘤坏死因子相关蛋白9(C1q/TNF-related protein,CTRP-9),同型半胱氨酸(Hcy)的干预作用,以及对糖尿病模型大鼠血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),趋化因子5(chemokine(C-X-C motif)ligand5,CXCL-5)的影响,探讨炎症指标与T2DM的相关性以及炎症反应导致T2DM血管病变的机理,评价DJC抑制炎症反应,防治和延缓糖尿病血管并发症的作用靶点和机理。方法:1.临床研究1.1研究对象:选择2014年6至2015年6月安徽中医药大学第一附属医院健康体检者30例和2型糖尿病患者60例。按照随机数字表法将糖尿病患者分为对照组30例和治疗组30例。对照组和治疗组按常规予西药口服降糖治疗,治疗组在西药治疗的同时,加服丹蛭降糖胶囊,两组疗程均为3个月(12周)。1.2研究方法:分别计算治疗前后两组患者的中医证候积分,检测空腹血糖(FPG)、餐后2小时血糖(2hPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、C肽、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL),计算胰岛素抵抗指数(IRI),检测血清Hcy、CTRP-9水平。检测治疗后对照组、治疗组患者血中Hcy、CTRP-9表达水平,比较治疗后两组的差异。2.动物实验2.1研究对象:将55只大鼠适应性喂养1周后,随机选出10只做为空白组,其余为高脂饲料组。空白组喂以普通饲料,高脂饲料组喂以高脂饲料,4周后,高脂饲料组大鼠腹腔注射链脲佐菌素(STZ)35 mg/kg,诱发糖尿病模型。模型诱发成功后,将大鼠随机分为4组:模型组12只,丹蛭高剂量组11只,丹蛭低剂量组组11只以及吡格列酮组11只,全部大鼠均连续灌胃治疗8周。2.2研究方法:观察治疗前后大鼠行为活动、精神状态、是否易激惹、毛发光泽、体重变化、摄食及饮水量等一般情况,检测大鼠FPG、TC、TG等水平;处死大鼠,取腹主动脉血用ELISA法检测血清TNF-α和CXCL-5水平。结果:1.临床研究结果临床研究发现,治疗12周后,总有效率治疗组85.7%,对照组55.2%,治疗组疗效优于对照组(P0.05);两组患者治疗后,FPG、2hPG、HbA1c、FINS、2hINS、F-C、2hF-C均较治疗前显著改善(P0.01);治疗前与治疗后相比,对照组和治疗组TG、LDL、HDL均有明显改善(P0.01);治疗12周后治疗组和对照组CTRP-9、Hcy水平均较治疗前明显改善(P0.01),治疗后二组相比,CTRP-9、Hcy水平有统计意义(P0.05或P0.01)。2.动物实验结果动物实验结果表明,造模前后大鼠体重无明显变化(P0.05);造模成功后,各组大鼠体重比造模前略有降低(P0.05),治疗后,丹蛭高剂量组和吡格列酮组大鼠体重较造模后显著增加(P0.01),模型组较正常组降低(P0.05),丹蛭高剂量组和吡格列酮组均较模型组体重明显降低(P0.05或(P0.01)。模型组、吡格列酮组及丹蛭组大鼠造模后摄食量、饮水量及血脂水平均较空白组增加(P0.01),治疗后丹蛭组摄食量及饮水量均低于模型组(P0.01),与造模成功后相比,第2、4、8周末,模型组血糖无明显波动(P0.05),然丹蛭高、低剂量组与吡格列酮组均较造模后显著降低(P0.01),然而各药物组之间无明显差异(P0.05)。与正常对照组相比,模型组TNF-α与CXCL-5水平显著升高(P0.01);治疗后,与模型组比较,丹蛭降糖胶囊高、低剂量组TNF-α、CXCL-5水平显著降低(P0.01),吡格列酮组与丹蛭组比较无差异(P0.05)。结论:丹蛭降糖胶囊能显著改善2型糖尿病中医临床症状及相关炎症指标,其机制可能与调节糖脂代谢、改善胰岛素抵抗、升高CTRP-9,降低Hcy含量、下调TNF-α和CXCL-5的表达有关。
[Abstract]:Objective: To observe the effect of DJC on complement C1q/ TNF-related protein 9 (CTRP-9) and homocysteine (Hcy) in type 2 diabetes mellitus (T2DM). as well as the effects of tumor necrosis factor-jun (tnf), chemotactic factor 5 (c-x-c motif) ligand5, cxcl-5) on serum tumor necrosis factor-jun (tnf), chemotactic factor 5 (c-x-c motif) ligand5, cxcl-5) in diabetic model rats. and aims to prevent and delay the action target and mechanism of diabetic vascular complications. Method: 1. Clinical Study 1. 1 Study Object: Select 30 patients and 60 patients with type 2 diabetes from June 2014 to June 2015 in the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. The diabetic patients were divided into 30 cases of control group and 30 cases of treatment group according to the random number table method. The control group and the treatment group were treated orally with western medicine. The treatment group was treated with western medicine. The treatment group was treated with western medicine. Both groups were treated with Danjiangtang capsule. The two groups were treated for 3 months (12 weeks). Blood glucose (2hPG), glycated hemoglobin (HbA1c), fasting insulin (FINS), C-peptide, total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), calculated insulin resistance index (IRI), serum Hcy, CTRP-9 level. The levels of Hcy and CTRP-9 in the blood of the treated group and the treated group were compared with those of the control group. Animal experiment 2. 1: After 1 week adaptation of 55 rats, 10 rats were randomly selected as blank group and the rest were high fat feed group. The rats fed with normal diet and high fat diet were fed with high fat feed for 4 weeks, and the rats were injected into the abdominal cavity of high fat diet group (STZ) at 35 mg/ kg to induce the model of diabetes. After the model induction was successful, rats were randomly divided into 4 groups: 12 in the model group, 11 in the high dose group of the Danone group, 11 in the low dose group of Danone and 11 in the oxycodone group, and all the rats were given a continuous intragastric gavage for 8 weeks. 2. Methods: The behavior and mental state of the rats before and after treatment were observed. The levels of FPG, TC, TG, etc. were detected in rats. The levels of serum TNF-CA125 and CXCL-5 were detected by ELISA. Result: 1. The results of clinical study showed that after 12 weeks of treatment, 85.7% of total effective treatment group and 51.2% in control group, and the curative effect of treatment group was better than that of control group (P0.05). The levels of CTRP-9 and Hcy in the treatment group and the control group were significantly improved before and after treatment (P0.01). The levels of CTRP-9 and Hcy in the treatment group and the control group were significantly improved before treatment (P <0.01). The levels of CTRP-9 and Hcy were statistically significant (P <0.01). Animal experiment results showed that there was no significant change in weight of rats before and after the model (P0.05). After the model was successful, the body weight of each group decreased slightly before the model (P0.05). Compared with the normal group (P0.05), the body weight of the model group was significantly lower than that in the model group (P0.05 or P0.01). Compared with the model group (P0.01), the food consumption, drinking water volume and blood fat level were lower in the model group (P <0.01) than those in the model group (P0.01). There was no significant fluctuation in blood glucose in model group (P0.05). Compared with the normal control group, the levels of TNF-PAF and CXCL-5 in the model group were significantly higher than that of the normal control group (P0.01). After treatment, the levels of TNF-and CXCL-5 in the high and low dose groups were significantly lower than those of the model group (P0.01). Conclusion: Danzhijiangtang capsule can significantly improve the clinical symptoms and related inflammatory indexes of type 2 diabetes. The mechanism may be related to the regulation of insulin metabolism, improve insulin resistance, increase CTRP-9, decrease Hcy content, and down-regulate the expression of TNF-PAF and CXCL-5.
【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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