摘要
第一部分文献研究
糖尿病(diabetes mellitus,DM)是一种由多病因引起以糖脂代谢紊乱的内分泌系统疾病。随着饮食结构,生活方式的改变,世界糖尿病人口呈现急剧上升的的趋势,但是却未能找到根本性的治疗药物。许多研究表明,氧化应激和糖尿病密切相关,在糖尿病的发生发展起到重要作用,贯穿糖尿病及其并发症整个过程,是胰岛素抵抗,糖尿病及心血管疾病的共同土壤。因此糖尿病抗氧化治疗领域成为当今研究的热点之一
中医药治疗糖尿病具有整体调节的特色,其疗效显著,副作用少,而且远期疗效亦较稳定,具有比西药更大的优势。本学科早在上世纪80年代就开展了对2型糖尿病的中医防治研究,围绕气阴不足、瘀血阻络的病机,采用经方桃核承气汤为基础加味研制成降糖三黄片,在临床上治疗2型糖尿病取得显著疗效。进一步从抗氧化角度研究降糖三黄片对于糖尿病以及慢性并发症的疗效及作用机制对于其在临床的广泛应用具有深远的意义。
第二部分实验研究
目的：观察中药降糖三黄片对糖尿病大鼠胰腺抗氧化的影响,从抗氧化机制入手探讨降糖三黄片对糖尿病的治疗作用及其作用机理。
方法：清洁级Wistar大鼠普通饲料适应性喂养1W后,改用高脂高热量饲料喂养一个月。除正常组外其余均按30mg/kg腹腔注射STZ进行造模,连续两次空腹血糖=11.1mmol/L,查尿糖++以上,胰岛素敏感指数降低,且有多饮、多尿、多食现象确认为2型糖尿病模型。造模成功后再进一步细分为模型组,中药干预组,西药干预组。中药组以降糖三黄片药量按787.5mg/kg/d的剂量进行治疗,西药组以二甲双胍组药量按照157.5mg/kg/d的剂量进行治疗,正常组及模型组灌服等量蒸馏水,继续喂养8W。①实验期间比较各组大鼠一般情况②通过比较造模后1周与实验末的FBG、CHO和TG以及胰岛素改变,探讨降糖三黄片对糖脂代谢的作用。③造模后8W实验结束,处死大鼠取胰腺组织,测定各组SOD,MDA,GSH等氧化指标,考察降糖三黄片对抗氧化体系的影响。④造模后8W实验结束,处死大鼠取胰腺组织,光镜观察降糖三黄片对大鼠胰腺组织保护作用。
结果：①一般情况比较：模型组大鼠较正常组欠活泼,多精神萎靡；皮毛明显缺少光泽,色灰黄。造模后24h,模型组大鼠即出现尿量明显增加,其后摄食量及饮水量较正常组大鼠逐渐增加。正常组大鼠体重逐渐增加,模型的各组大鼠体重在造模后1周与正常组大鼠有显著差异(P<0.01)；至实验末模型组和西药组体重明显低于正常组,有显著差异(P<0.01)而中药组体重明显高于西药组,两者相比具有显著差异(P<0.01)。②生化指标比较：造模后1周各组的血糖、血脂升高、胰岛素敏感指数下降,同正常组相比具有显著性差异(P<0.01),实验末降糖三黄片组血糖、血脂水平明显下降,胰岛素敏感指数上升,同模型组比较有显著性差异(P<0.05)③抗氧化比较,模型组SOD活力较正常组显著降低,具有统计学差异(P<0.01),中药及西药治疗后,SOD活力指数都有上升,以中药组效果更为明显,具统计学差异(P<0.01)。模型组MDA指数高于正常组,在使用中药及西药治疗后,MDA含量都有下降,以中药组下降较为明显,但以上指数都不具统计学意义。模型组含量GSH指数明显低于正常组,具有统计学差异(P<0.05),经过中药及西药治疗后,GSH都有上升,具有统计学差异(P<0.05)以西药组上升较为明显④病理结果表明模型组模型组胰岛平均横截面积较正常组显著减小(P<0.05)；。模型组胰岛细胞变性坏死与正常组比较具有显著差异(P<0.05)。
结论：①中药降糖三黄片从指标显示可以降低糖尿病大鼠的血糖、血脂水平,改善胰岛素抵抗,还能够明显改善糖尿病大鼠“三多一少”的状态,体现了中医学整体观念的特点。②中药降糖三黄片能增加胰腺抗氧化能力,其抗氧化能力与西药二甲双胍相似。③中药降糖三黄片能改善STZ破坏的胰岛截面积。增加胰岛细胞计数,效果优于西药二甲双胍,
Part 1:Literature research
Diabetes Mellitus(DM) is a kind of endocrine system disease caused by multiple pathogenesis, leading to glycolipid metabolic disorder. With the change of diet structure and lifestyle, worldwide DM population has a dramatic increase tendency. However, no curative drugs have been found so far. Many researches indicated that oxidative stress has a close relationship with DM. It is playing an important role in the occurrence and development of DM. Oxidative stress is the common cause to insulin resistance, DM and cardiovascular diseases. Antioxidant therapy in DM treatment has become a hot spot nowadays.
Traditional Chinese Medicine (TCM) in treating DM has a characteristic of overall regulation. It has a curative and stable effect and more superior advantages than western medicine. Our subject has been on the research for T2DM prevention and treatment for more than 30 years. On the pathogenesis of qi-yin deficiency, blood stasis obstructs the channel, we developed Jiangtangsanhuang Pill on the basis of the classical prescription:Taohe Chengqi Decoction. There are many curative effects on T2DM with Jiangtangsanhuang Pill in the clinic. The aim is to research the effects and mechanisms of DM as well as its complications in the aspect of oxidative stress, excavate the far-reaching significance in the clinic.
Part 2:Experimental Research
Objective:
To observe the influence of antioxidative stress on Jiangtangsanhuang Pill in the pancreases of the diabetic rats. To investigate the curative effects and mechanisms of Jiangtangsanhuang Pill in the oxidized mechanism way.
Methods:
Wistar rats were fed up with common diet. After 1 week the common diet was replaced by high cholesterol diet. The rats were intraperitoneal injected STZ for 30mg/kg except those in normal group. The characteristics of diabetic rats were that fasting blood glucose (FBG)≥11.1mmol/L at two different times, positive of urine glucose for more than two "+", Insulin Sensitive Index (ISI) decreased, with polydipsia, polyphagia and polyuria symptms. After modeling, the rats were divided into several groups, including model group, Chinese medicine intervention group and western medicine intervention group, Jiangtangsanhuang Pill was intragastric adminstrated as 787.5mg·kg-1·d-1 in Chinese medicine intervention group, while metformin was as 157.5mg·kg-1·d-1 in western medicine intervention group, the same amount of distilled water was intragastric administrated respectively in normal group and model group. The duration of experiment was 8 weeks.①To compare the rats'health state during the experiment.②To compare the changes of FBG, CHO and TG of different times and researched the function of Jiangtangsanhuang Pill on glucolipid metabolism.③After 8 weeks, the rats were killed and the pancreatic tissues were detected for SOD, MDA, GSH. To observe the impact of Jiangtangsanhuang Pill on antioxidative systems.④To observe Jiangtangsanhuang Pill's protective effect on pancreatic tissues.
Results:
①Health state:Compared with normal group, the rats in model group were less active,more apathetic, the colour of the fur was grey and yellow and lack of luster. 24 hours after modeling, the rats'urine and appetite increased significantly in model group, while the weight decreased 48 hours after injecting STZ. The rats'weight in the normal group increased gradually. After 72 hours to 1 week, all the rats'weight came to stable. After one week, the weight in normal group and model group had a significant difference (p<0.01); By the end of the experiment, the weight in model and western medicine group was lower than that in normal group, which had a significant difference (p<0.01); the weight in Chinese medicine group was higher than that in western medicine group, they had a significant difference(p<0.01).②Biochemical indicator:1 week after modeling, the blood glucose and cholesterol increased and the Insulin Sensitive Index (ISI) decreased. It had a significant difference comparing with normal group (p<0.01). At the end of the experiment, the blood glucose and cholesterol decreased and the ISI increased, which had a significant difference comparing with model group (p<0.05).③comparison of antioxidation:The SOD activity in model group decreased significantly comparing with that in normal group, which had a significant difference (P<0.01). The SOD index increased with both Chinese and western medicine treatment, but the decrease in Chinese medicine group was more significant. They had statistical significance. The MDA in model group was higher than that in normal group. MDA level began to decrease with the treatment of Chinese medicine and western medicine. The decrease in Chinese medicine group was more significant. However, they did not have statistical significance. GSH in model group was lower than that in normal group, which had statistical significance (p<0.05), GSH increased in Chinese and western medicine treatment, they both had statistical significance. Chinese medicine group (p<0.05) was more superior than which in western medicine (p<0.05).④Pathological results showed that the average cross-sectional area of pancreatic island decreased significantly in model group than that in normal group. Comparing with normal group, islet cells degeneration in model group had a significant difference (P<0.05).
Conclusion:
①ccording to relevant index, Jiangtangsanhuang Pill can decrease the level of diabetic rats'blood glucose and cholesterol, improve insulin resistance and the diabetic symptoms. It showed holism concept in TCM vividly.②Jiangtangsanhuang Pill can strengthen pancreas'capacity in antioxidation, the effect of which was the same to metformin.③Jiangtangsanhuang Pill can improve cross-sectional area of islet island destroyed by STZ. It also can increase islet cell counting, which effect is more superior than metformin.
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