小型猪实验动物化和糖尿病模型及中药“脾胃康”作用研究

发布时间：2018-01-02 00:04

本文关键词：小型猪实验动物化和糖尿病模型及中药“脾胃康”作用研究　出处：《广州中医药大学》2005年博士论文　论文类型：学位论文

【摘要】：糖尿病(diabetes mellitus,DM)中医又称为“消渴病”或“消瘅”,是由胰岛素合成与分泌减少,或胰岛素受体及受体后功能障碍而引起的以高血糖为生化特征的一种常见内分泌代谢疾病。小型猪体型小、遗传性能稳定、器官功能和组织结构与人体相似度大,具有杂食性,实验环境和条件易于控制。在我国小型猪资源较为丰富,适于作医学动物实验的有五指山微型猪、环江香猪、巴马小型猪、西双版纳小型猪、芷猪等品种/品系。广西巴马小型猪24项血液生理指标中有14项与人类相似,表明巴马小型猪生理功能与人具有相似性。SPF小型猪的血液、尿液生理生化参考值变动幅度小,SPF小型猪血液成分变化趋势与SPF大、小鼠血液成分变化趋势一致。链脲佐菌素(STZ)能够选择性地破坏某些种属动物胰岛的β细胞,导致糖尿病的发生。四氧嘧啶(Alloxan)40mg/Kg体重腹腔注射,配以高糖饲料复制出糖尿病胃肠动力障碍模型。细胞凋亡在糖尿病并发症的发生中发挥重要作用,在高血糖状态下,抗凋亡基因Bcl-2表达降低,而促凋亡基因Bax表达增加,导致细胞凋亡数目增加。通过对细胞凋亡的调控机制的研究,可望找到延缓或逆转细胞凋亡,防治糖尿病及其并发症的方法。中医学认为糖尿病属阴虚燥热,以阴虚为本,以燥热为标,与肺脾(胃)肾三脏相关。脾胃功能失调、脾气虚弱是糖尿病的病机。有“脾虚病机论”、“治脾论”、“调理脾胃升降治糖尿病”等观点。糖尿病性胃病或以症状命名,如“痞满”、“噫气”、“痰饮”;或据病机将本病诊为“胃缓”,因中虚气滞,通降无力而致。资料表明,患者胃排空延迟,出现厌食、打呃、腹胀等临床症状。中医提出补气健脾、和胃理气,益气养阴、行气活血和醒脾运脾等治则治法,具有显著临床疗效。糖尿病胃病属本虚标实之证。治疗时应予具有健脾理气、活血化瘀适当加用益肾、养胃作用的方药。中药复方“脾胃康”是根据糖尿病胃病发病机制及中医治则研制并使用的经验方,临床应用疗效显著。为了探讨建立小型猪糖尿病模型的程序和方法,进一步研究糖尿病并发症的发病机制,揭示中药复方“脾胃康”的药物作用机理,特开展了本实验研究。本研究旨在通过对广西巴马小型猪的生理、生化指标及其在不同时期的生长变化、消化道组织的超微结构进行研究,探讨巴马小型猪的实验动物化;建立小型猪胃电极埋植手术操作程序和胃电检测方法,检测小型猪的胃电参考数据及其变化规律;对小型猪进行糖尿病模型复制试验,探讨初步建立小型猪糖尿病模型的复制方法;观测糖尿病大鼠胃组织的病理改变和凋亡相关基因Bax、Bcl-2蛋白表达变化,探讨中药复方“脾胃康”的作用机制。巴马小型猪3月龄时平均体重为2.87±0.58kg,体长34.29±4.35cm。12月龄时平均体重达到6.50±0.44kg,体长达到66.67±4.03cm。到18月龄平均体重和
[Abstract]:Diabetes (diabetes mellitus, DM) of traditional Chinese medicine is also called "diabetes" or "Xiaodan", is composed of insulin synthesis and secretion reduced, or dysfunction of the insulin receptor and post receptor induced by high glucose as the biochemical features of a kind of common endocrine and metabolic diseases.
Pigs are small, genetic stability, organ function and tissue structure with human similarity, is omnivorous, the experimental environment and the condition is easy to control. In the small pig resource in China is relatively rich, suitable for medical animal experiments with Five Fingers Group miniature pig, Huanjiang pig, Bama miniature pig, Xishuangbanna pig, pig Zhi varieties / lines. 24 blood physiological index of Guangxi Bama miniature pig in 14 and that is similar to that of human physiological function of Bama miniature pigs and people with similar.SPF mini pig's blood, urine, physiological and biochemical changes in small amplitude of the reference value, SPF mini pig blood composition change trend and SPF, changes of blood components in mice the same trend. Streptozotocin (STZ) can selectively destroy certain species of animal pancreatic beta cells, leading to the occurrence of diabetes. Four alloxan (Alloxan) 40mg/Kg intraperitoneal injection, with high sugar diet complex A model of diabetic gastrointestinal motility disorders. Apoptosis plays an important role in the occurrence of complications of diabetes, high blood sugar condition, anti apoptosis gene Bcl-2 expression decreased, while the expression of apoptotic gene Bax increased, resulting in cell apoptosis. The increase in the number of study on the mechanism of regulation on cell apoptosis, may be found to delay or reverse the apoptosis methods, prevention and treatment of diabetes and its complications.
Traditional Chinese medicine thinks that diabetes is Yin scorching, yin deficiency, the standard for heat, spleen (stomach) and lung kidney three dirty. Dysfunction of spleen and stomach, spleen qi deficiency is the pathogenesis of diabetes. "The pathogenesis theory", "Treat Spleen", "spleen and stomach and treat diabetes" concept. Diabetic gastropathy or in the name of symptoms, such as "fullness", "Yi Qi", "phlegm"; or according to the pathogenesis of the disease will be diagnosed as "stomach slow", because the virtual stagnation, Tongjiang and weakness.
Data show that the delayed gastric emptying in patients with anorexia, abdominal distension, hiccup, clinical symptoms of TCM. The spleen and stomach, Qi, tonifying qi and nourishing Yin, Qi and blood, spleen and spleen treatment, with significant clinical efficacy. Diabetic gastropathy is superficiality syndrome. Treatment should be with Spleen Qi. Appropriate with Yishen Huoxue Huayu Decoction, Yangwei effect. The traditional Chinese medicine "piweikang" is the experience according to the pathogenesis of diabetic gastropathy and TCM development and use, clinical curative effect is remarkable.
In order to explore the procedure and method of establishing miniature pig diabetes model, we further studied the pathogenesis of diabetic complications, and revealed the mechanism of Chinese herbal compound "spleen stomach Kang".
The purpose of this study is to through the physiology of Guangxi Bama mini pig, biochemical index and growth in different periods, to study the ultrastructure of gastrointestinal tissue, explore the Bama miniature pig experimental animal; establishment of miniature pig gastric electrode implantation operation procedure and gastric electrical detection method, detection of porcine gastric electrical reference data and changes; replicate test model of diabetes on mini pigs, replication method study of the establishment of diabetic model in pigs; pathological change and apoptosis related gene Bax in gastric tissue observed in diabetic rats, the expression changes of Bcl-2 protein, and to explore the mechanism of traditional Chinese medicine "piweikang".
The average body weight of Bama miniature pigs is 2.87 + 0.58kg, the body length is 34.29 + 4.35cm.12, the average body weight reaches 6.50 + 0.44kg at the age of the month, and the body length reaches 66.67 + 4.03cm. to 18 month old, the average body weight is 3 month old.

【学位授予单位】：广州中医药大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R-332;R285

【引证文献】