化瘀降浊合剂干预代谢综合征的疗效评价及其对部分致动脉粥样硬化因子的影响

【作者】 周晖；

【导师】 王玉来； 高彦彬；

【作者基本信息】 北京中医药大学 ， 中医内科， 2007， 博士

【摘要】 本论文包括文献综述、临床研究和实验研究三部分内容。在文献综述部分系统回顾了近20年来国内外中西医在代谢综合征(MS)的临床和基础研究方面的进展情况。比较全面地反映了当今对MS流行病学、诊断、评价方法、发病机制、临床危害和干预措施等方面的研究现状和发展趋势,总结了现代中医药学家对MS在病因病机、分证论治、中医药干预和中药作用机制研究等方面的进展情况,简要分析了目前研究中存在的问题和薄弱环节,展望了中医药干预MS的发展方向和可能的切入点。在临床研究部分观察了化瘀降浊合剂治疗代谢综合征的疗效及其对部分致动脉粥样硬化危险因子的影响。本研究选择符合2005年国际糖尿病联盟定义且辨证为湿浊血瘀证候的MS患者70名,随机分为中药治疗组35例,西药对照组35例,中药治疗组给予化瘀降浊合剂治疗,对照组给予马来酸罗格列酮治疗,连续治疗8周。治疗前后分别观察了患者的临床症状、体重指数(BMI)、腰臀比(WHR)、血糖、血脂、血压、胰岛素作用指数(IAI)、胰岛素抵抗指数(HOMA-IR)、超敏C反应蛋白(hs-CRP)、同型半胱氨酸、纤维蛋白原、尿白蛋白排泄率、肱动脉舒张功能和不良反应。结果显示,化瘀降浊合剂可有效改善MS患者的临床症状(P<0.05),中医证候疗效总有效率为78.79%,明显优于对照组(P<0.05)。对轻中度高血糖和脂代谢紊乱有明显的改善作用(P<0.05),与马来酸罗格列酮的作用相似(P>0.05)。化瘀降浊合剂与马来酸罗格列酮对血压都有轻度改善作用,同时化瘀降浊合剂可以降低脉压差,与治疗前比较有统计学差异(P<0.05)。治疗后两组的IAI均有提高,HOMA-IR均有下降,与治疗前比较有统计学差异(P<0.05),而组间比较无统计学差异(P>0.05),提示化瘀降浊合剂具有与马来酸罗格列酮相近的改善胰岛素抵抗的作用。另外,化瘀降浊合剂可显著降低hs-CRP、同型半胱氨酸、纤维蛋白原、尿白蛋白排泄率,改善肱动脉舒张功能,对这些致动脉粥样硬化危险因子的改善作用提示化瘀降浊合剂可能具有预防或延缓动脉粥样硬化发生和进展的作用。在观察期内未发现中药的明显不良反应及肝肾副作用。在实验研究中采用高脂高盐饲料喂养的方法建立了胰岛素抵抗大鼠模型。观察了化瘀降浊合剂对胰岛素抵抗大鼠体重、糖脂代谢、血压、胰岛素敏感性、血清肿瘤坏死因子-α(TNF-α)和脂联素等影响以及脂肪组织中TNF-αmRNA和脂联素mRNA表达水平的影响。结果显示,化瘀降浊合剂可显著抑制胰岛素抵抗大鼠体重的增长,明显优于西药组(P<0.05),中药组大鼠的体重增长速度与空白对照组相近;明显改善糖脂代谢紊乱和胰岛素敏感性(P<0.05),与罗格列酮作用相近(P>0.05);轻度降低血压,但无统计学差异;抑制脂肪组织TNF-αmRNA的表达而降低血清TNF-α水平;促进脂肪组织脂联素mRNA的表达而升高血清脂联素水平。综合以上研究结果认为,化瘀降浊合剂具有改善糖脂代谢和胰岛素敏感性的作用,具有明显的抗炎作用和升高血管保护因子脂联素的作用,这些作用在改善胰岛素抵抗,纠正代谢紊乱的同时有利于血管内皮的保护,可预防或延缓动脉粥样硬化的发生和发展。更多还原

【Abstract】 My thesis includes three parts: literature summarization, clinical observation and experimental research.The part of literature summarization reviews the progress of clinical and experimental research on treating metabolic syndrome (MS), including the aspects of Western Medicine and Traditional Chinese Medicine (TCM). This part reflects the status quo of researches on epidemiology, diagnosis, evaluation criteria, pathogenesis, clinical features and intervention. It also summarizes the knowledge of scholars of TCM on the etiology, pathogenesis, differentiation of TCM syndrome, and TCM intervention and mechanism. Unsolved problems, weak points and possible solution of researches on MS are also analyzed in this part.Clinical research was performed to observe the clinical efficiency of HuaYu JiangZhuo Mixture (HYJZM) on MS and its effect on pro-atherosclerosis risk factors. 70 MS patients conforming to 2005 definition given by International Diabetes Federation (IDF) were randomly divided into two groups: HYJZM-treated group (n=35) and western medicine- treated group (n=35). The patients were identified as the syndrome of blood stasis and phlegm-dampness and treated with HYJZM or Rosiglitazone for 8 weeks. Clinical symptom, body mass index (BMI), waist-hip ratio (WHR), fasting plasma glucose (FPG), two hour plasma glucose (2hPG), blood pressure (BP), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), insulin action index (IAI), high sensitive C reactive protein (hs-CRP), homocysteine (Hcy), fibrinogen, urinary albumin excretion rate (UAER), brachial artery dilation and adverse reaction were observed before and after treatment for the two groups. Results showed that clinical manifestation of HYJZM-treated group was improved significantly (P<0.05). The total efficiency of HYJZM on TCM syndrome was as high as 78.79%, which was higher than that of Rosiglitazone- treated group (P<0.05). Hyperglycemia and lipid metabolism disturbance were improved in both HYJZM- and Rosiglitazone-treated groups (P<0.05) and there was no statistical significance between these two groups. BP in both groups was slightly lowered, showing no difference when compared with that before treatment. Pulse pressure was decreased in HYJZM-treated group, which was lower than that before treatment (P<0.05). IAI was augmented in both groups, suggesting that HYJZM and Rosiglitazone have similar improving effects on insulin resistance. The plasma levels of hs-CRP, Hcy, fibrinogen, and UAER were decreased and brachial artery dilation was improved when treated with HYJZM. These data support the notion that HYJZM may protest against the process of atherosclerosis through controlling pro-atherosclerosis risk factors. No obvious adverse reaction and side effect were observed in HYJZM-treated group. Rat insulin resistance model was established through feeding a high-fat-salt diet. The effects of HYJZM on body weight, glucose and lipid metabolism, BP, IAI were observed. Serum levels and mRNA expressions in adipose tissue of TNF-αand adiponectin were also investigated. Results showed that HYJZM treatment suppressed the increase of body weight significantly, which was better than Rosiglitazone treatment. HYJZM and Rosiglitazone had similar improving effects on glucose and lipid metabolism disturbance and insulin sensitivity. BP was lowered slightly in HYJZM-treated group (P>0.05). HYJZM suppressed the mRNA expression of TNF-αin adipose tissue and lowered the serum level of TNF-α. Furthermore, the mRNA expression in adipose tissue and serum level of adiponectin were promoted in HYJZM-treated group. Taken together, HYJZM has improving effect on glucose and lipid metabolism and insulin sensitivity. HYJZM treatment augments adiponectin level and exerts anti-inflammatory effect. These results suggest that HYJZM may prevent the development and progress of atherosclerosis through protecting the function of vascular endothelia.更多还原