【摘要】：目的:微循環(huán)障礙的病理表現(xiàn)存在于心腦血管疾病、糖尿病、腫瘤等諸多高危的疾病,微循環(huán)障礙與中醫(yī)的血瘀證有著密切的聯(lián)系,充分發(fā)揮中醫(yī)藥的優(yōu)勢,治療微循環(huán)障礙疾病具有重要的意義。本文觀察了膈下逐瘀湯及其拆方對與微循環(huán)障礙模型大鼠的療效及其機制,為進一步研究膈下逐瘀湯的影響,為臨床的用藥提供理論依據(jù)。方法:運用高分子右旋糖酐尾靜脈注射的方法制作大鼠微循環(huán)障礙模型。將50只Wistar大鼠隨機分為5組,每組10只,分別為正常對照組(簡稱“正常組”)、模型對照組(簡稱“模型組”)、膈下逐瘀湯高劑量組(簡稱“高劑量組”)、膈下逐瘀湯低劑量組(簡稱“低劑量組”)、活血拆方組(簡稱“拆方組”)。模型組、高劑量組、低劑量組、拆方組分別以10%高分子右旋糖酐進行尾靜脈注射,劑量10ml/Kg,隔天注射一次,連續(xù)注射10次。對照組隔天尾靜脈注射0.9%生理鹽水,劑量為10ml/Kg。給藥組在造�；A(chǔ)上,灌胃給藥,灌胃量為10ml/Kg,隔天灌胃一次,連續(xù)灌胃十次。其中,膈下逐瘀湯水煎液,低劑量組給藥量為7.5g/Kg,高劑量組給藥量為11.5 g/Kg;活血拆方組給于當歸、桃仁、紅花、川芎、元胡水煎液,每日用藥劑量為3g/Kg。對照組、模型組給于純凈水灌胃,灌胃量為10ml/Kg,隔天一次,共10次。末次給藥后,晚上動物禁食、不禁水,第2天進行實驗檢測。5%水合氯醛麻醉,首先進行腹腔腸系膜微循環(huán)觀察(主要檢測流速、流態(tài)、動靜脈比等,觀察有無血瘀改變;其次觀察有無出血等),其后抽取腹腔靜脈血,進行血液流變學、血管內(nèi)皮活性因子的檢測(NO、ET、VEGF、ES含量)等,探討微循環(huán)障礙、血瘀等改變的內(nèi)在機制。并取肝、肺等臟器組織進行肝、肺臟器組織病理檢測,重點觀察組織內(nèi)微循環(huán)損傷的改變。結(jié)果:膈下逐瘀湯高、低劑量組對微循環(huán)障礙大鼠有較好的療效,且活血拆方組效果不如全方組。(1)肺、肝組織微循環(huán)損傷的治療效果:第一,肺組織損傷的治療效果:給與膈下逐瘀湯后,高、低劑量組大鼠的間質(zhì)瘀血、出血狀況均明顯減輕,炎細胞浸潤明顯減少,間隔增厚的程度減輕,尤其是膈下逐瘀湯高劑量組肺組織微循環(huán)損傷的改善效果更為明顯,P0.05,結(jié)果具有統(tǒng)計學意義。拆方組的改善效果不如膈下逐瘀湯高、低劑量組,P0.05,結(jié)果具有統(tǒng)計學意義。其二,肝組織損傷的治療效果:膈下逐瘀湯高、低劑量組肝細胞比較均勻,無變性、壞死,肝小葉結(jié)構(gòu)較為清晰,肝臟纖維間隔恢復、紅細胞聚集之血瘀狀況得到了較好的改善,尤其是高劑量組的治療效果更為明顯。活血拆方組大鼠肝臟的微循環(huán)瘀血狀態(tài)也得到了改善,但效果不及高、低劑量組。(2)腸系膜微循環(huán)損傷的療效:膈下逐瘀湯高、低劑量組動、靜脈流速明顯上升,血液流態(tài)主要表現(xiàn)為線流,血流瘀滯狀態(tài)得到改善�；钛鸱浇M,血液流速升高,P0.05,結(jié)果具有統(tǒng)計學意義,腸系膜微循環(huán)狀態(tài)得到相應(yīng)的改善,但改善效果不如膈下逐瘀湯給藥組。膈下逐瘀湯高劑量組和低劑量組大鼠腸系膜微動脈增粗,微靜脈變細,DA/DV比值變大,P0.05,結(jié)果具有統(tǒng)計學意義,數(shù)據(jù)結(jié)果可顯示腸系膜血管壁受損得到改善,DA/DV比值接近正常組,腸系膜微循微循環(huán)狀況良好,且高劑量組的治療效果優(yōu)于低劑量組�；钛鸱浇M對腸系膜動、靜脈的病理狀況也有一定的療效,但治療效果不如膈下逐瘀湯全方組,P0.05,結(jié)果具有統(tǒng)計學意義。高劑量組和低劑量組出血像素點減少,出血面積小,出血癥狀得到較好的改善�；钛鸱浇M的治療效果不如膈下逐瘀湯的高、低劑量組。(3)對血流變指標的改善:膈下逐瘀湯高、低劑量組的全血高、低切粘度值以及血漿粘度值、全血高、低切還原粘度值、細胞壓積、紅細胞剛性指數(shù)、紅細胞聚集指數(shù)都有了明顯的降低,紅細胞變形指數(shù)(TK)出現(xiàn)了升高,P0.05,結(jié)果具有統(tǒng)計學意義,活血拆方組的治療效果不如膈下逐瘀湯給藥組。(4)對血管活性因子的療效:膈下逐瘀湯高、低劑量組NO含量升高,ET含量降低,差異具有統(tǒng)計學意義(P0.05),結(jié)果可表明血瘀的病理狀況明顯的減輕,微循環(huán)也得到較好的改善,且膈下逐瘀湯高劑量組的改善效果優(yōu)于低劑量組�；钛鸱浇M肺組織NO含量略有升高,ET含量顯著升高,NO與ET含量的比例嚴重失調(diào),但差異不具有統(tǒng)計學意義�；钛鸱浇M血漿中NO含量升高,ET含量有較大幅度的升高,且ET含量差異不具有統(tǒng)計學意義。膈下逐瘀湯高、低劑量組VEGF含量降低,ES含量升高,差異具有統(tǒng)計學意義(P0.05),結(jié)果可顯示肺組織損傷得到修復,肺部微循環(huán)狀況得到改善,且膈下逐瘀湯高劑量組的療效優(yōu)于低劑量組。拆方組與模型組比,拆方組VEGF含量顯著降低,ES含量升高,差異具有統(tǒng)計學意義(P0.05),可見活血拆方組對肺部損傷有一定的治療效果,但是治療效果遠不如膈下逐瘀湯高、低劑量組。大鼠血漿中VEGF和ES含量:從表中數(shù)據(jù)結(jié)果可以看出,正常組、模型組、膈下逐瘀湯高低及劑量組、活血拆方血漿中的VEGF含量極少,且結(jié)果差異不具有統(tǒng)計學意義。膈下逐瘀湯高、低劑量組大鼠血液中的ES含量減少,且高劑量組ES含量少于低劑量組,差異具有統(tǒng)計學意義(P0.05)�；钛鸱浇MES含量增多,差異具有統(tǒng)計學意義(P0.05)。結(jié)論:膈下逐瘀湯高、低劑量組對微循環(huán)障礙大鼠有較好的療效,且活血拆方組效果不如全方組,膈下逐瘀湯活血方藥與涼血止血藥及行氣藥的配伍作用是重要的。
[Abstract]:Objective: The pathological manifestations of microcirculation disorders are found in many high-risk diseases such as cardiovascular and cerebrovascular diseases, diabetes mellitus, tumor and so on. The microcirculation disorders are closely related to the blood stasis syndrome of TCM. It is of great significance to give full play to the advantages of TCM in treating microcirculation disorders. Methods: The rat model of microcirculation disorder was established by injecting high molecular dextran into tail vein. Fifty Wistar rats were randomly divided into 5 groups, 10 rats in each group, which were normal control group. Normal group, model control group (model group), high-dose group of Gexia Zhuyu Decoction (high-dose group), low-dose group of Gexia Zhuyu Decoction (low-dose group), and Huoxue Jiefang group (split prescription group). The control group was given 0.9% normal saline by tail vein every other day, and the dosage was 10ml/Kg. On the basis of modeling, the administration group was given intragastric administration with the dosage of 10ml/Kg, once every other day, continuously for ten times. Among them, the decoction of Gexia Zhuyu decoction, the dosage of low-dose group was 7.5g/Kg, and the dosage of high-dose group was 7.5g/Kg. The dosage was 11.5 g/Kg; the decoction of Angelica sinensis, Peach kernel, Safflower, Ligusticum Chuanxiong and Corydalis Corydalis were given to the decoction of Huoxue decoction, and the daily dosage was 3 g/Kg. The control group was given pure water by gastric lavage, and the dosage was 10 ml/Kg every other day. The microcirculation of mesenteric cavity was observed (mainly to detect the flow velocity, flow pattern, arteriovenous ratio, etc.) and the blood stasis was observed; the abdominal venous blood was then collected for Hemorheology and the detection of vascular endothelial active factors (NO, ET, VEGF, ES content) to explore the internal mechanism of microcirculation disturbance and blood stasis. Results: The high and low dose of Gexia Zhuyu decoction had better curative effect on rats with microcirculation disturbance, and the effect of Huoxue Jiefang group was not as good as that of the whole prescription group. (1) The therapeutic effect of lung and liver microcirculation injury: First, the treatment of lung tissue injury. Results: After giving Gexia Zhuyu Decoction, the interstitial blood stasis and bleeding of rats in high and low dosage groups were alleviated, inflammatory cell infiltration and interval thickening were significantly reduced, especially in the high dosage group, the improvement effect of pulmonary microcirculation injury was more obvious, P 0.05, the results were statistically significant. Second, the treatment effect of liver tissue injury: high-dose Gexia Zhuyu decoction, low-dose group liver cells more uniform, no degeneration, necrosis, liver lobule structure is clearer, liver fibrous septum recovery, red blood cell aggregation of blood stasis has been better improved, especially (2) The effect of mesenteric microcirculation injury: the velocity of arteries and veins in the high and low doses of Gexia Zhuyu Decoction increased significantly, and the blood flow pattern was mainly linear and blood stasis state. The results showed that the mesenteric microcirculation was improved correspondingly, but the improvement effect was not as good as that of the Gexia Zhuyu Decoction group. The results showed that the damage of mesenteric vascular wall was improved, the DA/DV ratio was close to the normal group, the mesenteric microcirculation was good, and the effect of high dose group was better than that of low dose group. The treatment effect of Huoxue Jiefang group was not as good as that of the high and low dose groups of Gexia Zhuyu Decoction. (3) Improvement of hemorheological indexes: high Gexia Zhuyu Decoction, high whole blood, low shear viscosity of low dose group. The values of plasma viscosity, whole blood viscosity, low shear reduction viscosity, hematocrit, erythrocyte stiffness index, erythrocyte aggregation index were significantly reduced, erythrocyte deformability index (TK) increased, P 0.05, the results were statistically significant, the effect of Huoxue Jiefang group was not as good as that of Gexia Zhuyu Decoction. The difference was statistically significant (P 0.05). The results showed that the pathological condition of blood stasis was obviously alleviated, and microcirculation was also improved. The improvement effect of high dose group was better than that of low dose group. The content of NO in lung tissue of Huoxue Jiefang group was slightly increased. The content of NO and ET in plasma increased significantly in Huoxue Decoction group, and the content of ET was not statistically significant. The content of VEGF and ES in Gexia Zhuyu Decoction were decreased in high and low dose groups, and the difference was statistically significant. The results showed that lung tissue injury was repaired, the microcirculation of lung was improved, and the curative effect of high dose group was better than that of low dose group. The content of VEGF and ES in plasma of rats: From the data of table, we can see that the content of VEGF in plasma of normal group, model group, high and low Gexia Zhuyu Decoction and dose group is very little, and the difference is not statistically significant. The content of ES in blood of rats in dose group decreased, and the content of ES in high dose group was less than that in low dose group, the difference was statistically significant (P 0.05). It is important that the compatibility of the decoction for removing blood stasis and activating blood and cooling blood and hemostasis drugs and Qi compatibility.
【學位授予單位】：山東中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R285.5

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