【摘要】：目的:觀察具有益氣養(yǎng)陰活血功效的丹蛭降糖膠囊(DJC)對(duì)2型糖尿病(T2DM)血管病變補(bǔ)體C1q/腫瘤壞死因子相關(guān)蛋白9(C1q/TNF-related protein,CTRP-9),同型半胱氨酸(Hcy)的干預(yù)作用,以及對(duì)糖尿病模型大鼠血清腫瘤壞死因子-α(tumor necrosis factor-α,TNF-α),趨化因子5(chemokine(C-X-C motif)ligand5,CXCL-5)的影響,探討炎癥指標(biāo)與T2DM的相關(guān)性以及炎癥反應(yīng)導(dǎo)致T2DM血管病變的機(jī)理,評(píng)價(jià)DJC抑制炎癥反應(yīng),防治和延緩糖尿病血管并發(fā)癥的作用靶點(diǎn)和機(jī)理。方法:1.臨床研究1.1研究對(duì)象:選擇2014年6至2015年6月安徽中醫(yī)藥大學(xué)第一附屬醫(yī)院健康體檢者30例和2型糖尿病患者60例。按照隨機(jī)數(shù)字表法將糖尿病患者分為對(duì)照組30例和治療組30例。對(duì)照組和治療組按常規(guī)予西藥口服降糖治療,治療組在西藥治療的同時(shí),加服丹蛭降糖膠囊,兩組療程均為3個(gè)月(12周)。1.2研究方法:分別計(jì)算治療前后兩組患者的中醫(yī)證候積分,檢測(cè)空腹血糖(FPG)、餐后2小時(shí)血糖(2hPG)、糖化血紅蛋白(HbA1c)、空腹胰島素(FINS)、C肽、總膽固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL),計(jì)算胰島素抵抗指數(shù)(IRI),檢測(cè)血清Hcy、CTRP-9水平。檢測(cè)治療后對(duì)照組、治療組患者血中Hcy、CTRP-9表達(dá)水平,比較治療后兩組的差異。2.動(dòng)物實(shí)驗(yàn)2.1研究對(duì)象:將55只大鼠適應(yīng)性喂養(yǎng)1周后,隨機(jī)選出10只做為空白組,其余為高脂飼料組。空白組喂以普通飼料,高脂飼料組喂以高脂飼料,4周后,高脂飼料組大鼠腹腔注射鏈脲佐菌素(STZ)35 mg/kg,誘發(fā)糖尿病模型。模型誘發(fā)成功后,將大鼠隨機(jī)分為4組:模型組12只,丹蛭高劑量組11只,丹蛭低劑量組組11只以及吡格列酮組11只,全部大鼠均連續(xù)灌胃治療8周。2.2研究方法:觀察治療前后大鼠行為活動(dòng)、精神狀態(tài)、是否易激惹、毛發(fā)光澤、體重變化、攝食及飲水量等一般情況,檢測(cè)大鼠FPG、TC、TG等水平;處死大鼠,取腹主動(dòng)脈血用ELISA法檢測(cè)血清TNF-α和CXCL-5水平。結(jié)果:1.臨床研究結(jié)果臨床研究發(fā)現(xiàn),治療12周后,總有效率治療組85.7%,對(duì)照組55.2%,治療組療效優(yōu)于對(duì)照組(P0.05);兩組患者治療后,FPG、2hPG、HbA1c、FINS、2hINS、F-C、2hF-C均較治療前顯著改善(P0.01);治療前與治療后相比,對(duì)照組和治療組TG、LDL、HDL均有明顯改善(P0.01);治療12周后治療組和對(duì)照組CTRP-9、Hcy水平均較治療前明顯改善(P0.01),治療后二組相比,CTRP-9、Hcy水平有統(tǒng)計(jì)意義(P0.05或P0.01)。2.動(dòng)物實(shí)驗(yàn)結(jié)果動(dòng)物實(shí)驗(yàn)結(jié)果表明,造模前后大鼠體重?zé)o明顯變化(P0.05);造模成功后,各組大鼠體重比造模前略有降低(P0.05),治療后,丹蛭高劑量組和吡格列酮組大鼠體重較造模后顯著增加(P0.01),模型組較正常組降低(P0.05),丹蛭高劑量組和吡格列酮組均較模型組體重明顯降低(P0.05或(P0.01)。模型組、吡格列酮組及丹蛭組大鼠造模后攝食量、飲水量及血脂水平均較空白組增加(P0.01),治療后丹蛭組攝食量及飲水量均低于模型組(P0.01),與造模成功后相比,第2、4、8周末,模型組血糖無(wú)明顯波動(dòng)(P0.05),然丹蛭高、低劑量組與吡格列酮組均較造模后顯著降低(P0.01),然而各藥物組之間無(wú)明顯差異(P0.05)。與正常對(duì)照組相比,模型組TNF-α與CXCL-5水平顯著升高(P0.01);治療后,與模型組比較,丹蛭降糖膠囊高、低劑量組TNF-α、CXCL-5水平顯著降低(P0.01),吡格列酮組與丹蛭組比較無(wú)差異(P0.05)。結(jié)論:丹蛭降糖膠囊能顯著改善2型糖尿病中醫(yī)臨床癥狀及相關(guān)炎癥指標(biāo),其機(jī)制可能與調(diào)節(jié)糖脂代謝、改善胰島素抵抗、升高CTRP-9,降低Hcy含量、下調(diào)TNF-α和CXCL-5的表達(dá)有關(guān)。
[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.
【學(xué)位授予單位】：安徽中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R259

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