【摘要】：目的：該實(shí)驗(yàn)通過(guò)腹腔注射鏈脲佐菌素（STZ）造糖尿病大鼠模型，并應(yīng)用益氣養(yǎng)陰活血方對(duì)成模的糖尿病大鼠進(jìn)行治療，觀察該藥對(duì)糖尿病大鼠的血糖、血脂、內(nèi)皮脂肪酶（EL）和大鼠胸主動(dòng)脈內(nèi)皮組織形態(tài)的影響，研究本方對(duì)成模糖尿病大鼠大血管病變的治療作用及可能的致病機(jī)制。 方法：選用雄性的清潔級(jí)wistar大鼠50只，體重230g～250g，普通飼料適應(yīng)性喂養(yǎng)4天后，采用完全隨機(jī)法將50只大鼠分為5組：正常組（N）6只，模型組（M）、中藥組（益氣養(yǎng)陰活血方組，Z）、西藥組（辛伐他汀組，X）、中藥+西藥組（益氣養(yǎng)陰活血方+辛伐他汀組，ZX）各11只。參考相關(guān)文獻(xiàn)，M、Z、X、ZX組大鼠給予濃度為1%的鏈脲佐菌素（STZ）檸檬酸緩沖液（檸檬酸緩沖液濃度為0.1mmol/L，pH4.5）按60mg/kg體重一次性腹腔注射，N組則給予相應(yīng)體積的1%檸檬酸-檸檬酸鈉溶液腹腔注射。72h后大鼠尾靜脈采血測(cè)血糖，若大鼠血糖超過(guò)16.7mmol/L，飲水量及尿量均顯著增多，則造模成功。Z組給予益氣養(yǎng)陰活血方按3.17ml/kg體重水煎濃縮液灌胃，X組給予辛伐他汀片濃縮液0.33mg/kg灌胃，ZX組上午給予與中藥組等量益氣養(yǎng)陰活血中藥，下午給予與西藥組等量辛伐他汀灌胃，N組與M組給予相應(yīng)中藥體積的生理鹽水灌胃，每日一次，共灌胃12周。于末次灌胃后禁食、禁水12h，2%戊巴比妥鈉按20mg/kg體重腹腔注射麻醉，斷頭取血，檢測(cè)血漿葡萄糖、總膽固醇、低密度脂蛋白膽固醇及高密度脂蛋白膽固醇。無(wú)菌操作取胸主動(dòng)脈1-2cm作為標(biāo)本，，置于4%的多聚甲醛溶液中固定，制作切片行HE染色，觀察血管內(nèi)皮組織變化情況，酶聯(lián)免疫吸附法檢測(cè)血清內(nèi)皮脂肪酶（EL）的水平。 結(jié)果： 1各組大鼠的一般情況 在實(shí)驗(yàn)過(guò)程中，N組大鼠精神飽滿，活動(dòng)自如，飲食、飲水、尿量均正常。M組大鼠則出現(xiàn)精神萎靡，明顯多飲、多食、多尿，體重逐漸減輕，毛色枯黃，反應(yīng)遲鈍等表現(xiàn)，符合糖尿病臨床“三多一少”的特征。各治療組大鼠表現(xiàn)介于正常組與模型組之間。偶有大鼠出現(xiàn)肢體活動(dòng)不利、皮膚潰爛等表現(xiàn)。M組、ZX組各死亡2只，Z組死亡1只。 2各組大鼠血糖水平的觀察 M組及各治療組大鼠血糖均增高，與正常組相比，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；X組與M組之間比較血糖變化不明顯，無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）；Z及ZX組與M組之間比較血糖降低，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；Z組與ZX組之間比較血糖變化不明顯，無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）。 3各組大鼠總膽固醇（TC）、高密度脂蛋白膽固醇（HDL）、低密度脂蛋白膽固醇（LDL）水平的觀察 M組及各治療組大鼠TC均增高，與正常組比較，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；Z組與M組之間比較TC變化不明顯，無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）；X組及ZX組與M組之間比較TC降低，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；X組與ZX組之間比較TC變化不明顯，無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）。 M組及各治療組大鼠LDL均增高，與正常組比較，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；Z組與M組之間比較LDL變化不明顯，無(wú)統(tǒng)計(jì)學(xué)意義（P0.05）；X組及ZX組與M組之間比較LDL降低，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；ZX組與X組比較，LDL降低，差別有統(tǒng)計(jì)學(xué)意義（P0.05）。 M組及各治療組與正常組大鼠之間比較，HDL明顯降低，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；各治療組與M組之間比較HDL明顯增高，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；三個(gè)治療組之間兩兩比較，HDL有明顯變化，差別有統(tǒng)計(jì)學(xué)意義（P0.05）。 4各組大鼠胸主動(dòng)脈內(nèi)皮組織形態(tài)的觀察 HE染色后N組內(nèi)皮細(xì)胞紋理清晰，走形正常，細(xì)胞漿著色均勻，胸主動(dòng)脈內(nèi)皮細(xì)胞扁平，內(nèi)膜光滑、平坦，中膜是平行相間排列的平滑肌細(xì)胞（smooth muscle cell，SMC）和彈力板。M組大鼠胸主動(dòng)脈內(nèi)膜呈局限性增厚且局部隆起，近內(nèi)膜的中膜平滑肌細(xì)胞可見(jiàn)增生及排列紊亂，增生平滑肌細(xì)胞處的彈力板排列不規(guī)則，呈波浪狀，偶可見(jiàn)彈力板斷裂、分離現(xiàn)象。各治療組大鼠胸主動(dòng)脈內(nèi)皮細(xì)胞的組織形態(tài)變化較模型組明顯減輕。 5各組大鼠酶聯(lián)免疫吸附法檢測(cè)血清內(nèi)皮脂肪酶（EL）表達(dá)的情況 M組及各治療組大鼠EL均增高，與正常組比較，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；各治療組與M組之間比較EL明顯降低，差別有統(tǒng)計(jì)學(xué)意義（P0.05）；三個(gè)治療組之間兩兩比較，EL有變化明顯，差別有統(tǒng)計(jì)學(xué)意義（P0.05）。 結(jié)論： l益氣養(yǎng)陰活血方可使糖尿病大鼠的一般狀態(tài)好轉(zhuǎn)，降低血糖，調(diào)節(jié)脂代謝。 2益氣養(yǎng)陰活血方可使糖尿病大鼠胸主動(dòng)脈內(nèi)皮組織的病理形態(tài)好轉(zhuǎn)，有治療糖尿病大血管內(nèi)皮病變的作用，可為臨床治療提供治療方案。 3益氣養(yǎng)陰活血方治療糖尿病大鼠大血管病變的作用可能與其能夠降低血糖，改善脂代謝，抑制血清內(nèi)皮脂肪酶（EL）表達(dá)的作用有關(guān)。
[Abstract]:Objective: To study the blood glucose and blood lipid of the diabetic rats by means of the experimental study of the model of diabetic rats by intraperitoneal injection of the streptozoin (STZ) and the treatment of diabetic rats with the effects of invigorating qi, nourishing yin and promoting blood circulation. The effects of endothelial lipase (EL) and the morphology of the endothelial tissue of the thoracic aorta in rats were studied, and the therapeutic effect and possible mechanism of the recipe on the large-vessel lesions of the model-type diabetic rats were studied. Methods: 50 rats were randomly divided into 5 groups: normal group (N) 6, model group (M), and traditional Chinese medicine group (qi-nourishing and yin-nourishing and blood-activating group). Z), western medicine group (simvastatin group, X), traditional Chinese medicine + western medicine group (Yiqi Yangyin Huoxue Fang + Simvastatin group, ZX) 1 1. Reference to the relevant literature, M, Z, X, ZX group, rats with a concentration of 1% of a chain-cometacin (STZ) citrate buffer (citric acid buffer at a concentration of 0. 1mmol/ L, pH 4.5) were used as one-time abdominal cavity at 60mg/ kg body weight The blood glucose of the rat tail vein was measured by intraperitoneal injection of the corresponding volume of 1% citric acid-sodium citrate solution, and the blood glucose was measured in the tail vein of the rat after 72h. If the blood sugar in the rat was more than 16.7mmol/ L and the amount of water and urine increased, the model was made. In the group of ZX group, the traditional Chinese medicine with the same amount of qi, nourishing yin, promoting blood circulation and promoting blood circulation was given in the morning of ZX group, and the same amount of simvastatin was given in the afternoon. In the group of Gavage, N and M, the volume of the corresponding Chinese traditional Chinese medicine was given intragastric administration, once a day, and a total of 1 was given by intragastric administration. 2 weeks. After the end of the stomach, the rats were fasted, and the water for 12h and 2% sodium pentobarbital was injected into the abdominal cavity by 20mg/ kg body weight. The blood was decapitated, and the plasma glucose, total cholesterol, low density lipoprotein cholesterol and high-density lipoprotein cholesterol were detected. Sterol. The thoracic aorta 1-2cm was taken as a specimen in a sterile operation, and was fixed in 4% paraformaldehyde solution. The section line HE staining was made to observe the changes of the vascular endothelial tissue. The enzyme-linked immunosorbent assay was used to detect the serum endothelial lipase (EL). Level. Results: 1 The general situation of the rats in each group was in the course of the experiment, and the rats in the N group were full of spirit and free of activity. The diet, drinking water and urine volume were all normal. The rats in the M group had the symptoms of listlessness, obvious polydipsia, polyphagia, polyuria, gradually reduced body weight, yellow and yellow hair, slow response and the like, and it was in accordance with the clinical

"three or one" of diabetes. The characteristics of s" . The performance of each treatment group in rats in between that normal group and the model group. there was a limb activity in the rat In group M, ZX group. There were 2 deaths and 1 death in the Z group. In group 2, the blood glucose level of the rats was higher than that of the normal group (P <0.05). The blood sugar changes between the group X and the M group were statistically significant (P0.05). There was no significant difference in blood glucose between Z and ZX groups (P <0.05), and the change of blood glucose between Z and ZX groups was not significant (P0.05). No significant, no statistical significance (P0.05). Total cholesterol (TC) and high-density lipoprotein cholesterol (HDL) in each group of rats (1) The level of low-density lipoprotein cholesterol (LDL) was higher than that in the treatment group. Compared with the normal group, the difference was statistically significant (P0.05); the difference between the group Z and the M group was not significant and there was no statistical significance (P0.05); the TC between the X group and the ZX group and the M group was lower and the difference was statistically significant (P0.05); and the difference between the X group and the ZX group was statistically significant (P0.05). There was no significant difference in the TC (P0.05). There was no significant difference in LDL in the M group and in the treatment group (P <0.05), and the difference between the group Z and the M group was not significant (P0.05), and the X group and the ZX group and the M group were not significant (P0.05). There was a significant difference between the group and the group (P <0.05), and the ZX group was the same as that of the group. In group X, LDL decreased and the difference was statistically significant (P0.05). The difference was significant between the treatment group and the control group (P <0.05), and the difference between the treatment group and the M group was significantly higher and the difference was statistically significant (P <0.05). (P0.05); between the three treatment groups There are significant changes in the HDL, and the difference is in series. The results showed that after HE staining, the endothelial cells of group N were clear in texture, normal in shape, uniform in color, flat in the endothelial cells of the thoracic aorta and smooth in the intima. in flat, that middle film is a parallel phase The smooth muscle cells (SMC) and the elastic plate were arranged in the middle membrane of the M group. The inner membrane of the rat thoracic aorta of the M group had the localized thickening and the local uplift and the smooth muscle cells of the inner membrane of the inner membrane were found to be hyperplastic and arranged, and the proliferation of the smooth muscle cells was increased. The elastic plates at the green smooth muscle cells are arranged irregularly, in a wave shape, and even visible elastic plates are broken The changes of the tissue morphology of the thoracic aortic endothelial cells in the treatment group were more than that of the model. The expression of serum endothelial lipase (EL) was detected by enzyme-linked immunosorbent assay (ELISA) in each group, and the levels of EL in all treatment groups were increased. Compared with the normal group, the difference was significant (P <0.05), and the difference between the treatment group and the M group was significantly lower (P <0.05), and the difference was significant (P 0. 0 5) There was a significant difference between the three treatment groups, and the difference was significant (P0. Conclusion: 1. The qi-tonifying and yin-nourishing blood-activating agent can improve the general condition of the diabetic rats, reduce the blood sugar and regulate the lipid metabolism. The qi-tonifying and yin-nourishing blood-activating agent can be used for invigorating qi and nourishing yin and promoting blood circulation. The pathological changes of the vascular endothelial tissue in the thoracic aorta of the diabetic rats have improved, and the effect of the treatment of the diabetic macrovascular endothelial diseases can be provided. The treatment scheme can be provided for clinical treatment.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R259

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 余歡歡;降糖消脂顆粒對(duì)2型糖尿病患者血管內(nèi)皮細(xì)胞功能影響[D];北京中醫(yī)藥大學(xué);2015年

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