【摘要】：目的:通過觀察動脈粥樣硬化大鼠模型肝臟及腹主動脈病理形態(tài)學改變,觀察對肝臟組織軟磷脂膽固醇�；D移酶(LCAT)、ATP結合盒轉運體A1(ABCA1)表達的影響,探討蘇木乙酸乙酯提取物對動脈粥樣硬化模型大鼠膽固醇逆轉運的影響,以及蘇木乙酸乙酯提取物防治動脈粥樣硬化的作用機制,為臨床應用蘇木提供實驗依據。方法:采用反復注射維生素D370萬IU(kg/d)及高脂飲食喂養(yǎng)的方法,誘導SD大鼠建立動脈粥樣硬化模型。成年大鼠40只,隨機分為4組,分別為空白對照組、模型對照組、蘇木乙酸乙酯提取物組、辛伐他汀組,每組10只,適應性喂養(yǎng)一周后,除空白對照組外余均腹腔注射維生素D370萬IU(kg/d)持續(xù)3日,同時喂養(yǎng)高脂飲食12周,建立動脈粥樣硬化模型。模型復制成功后各組連續(xù)給藥28天,取材。采用HE染色法觀察腹主動脈及肝臟病理形態(tài)學的變化,采用 RealTime PCR法觀察肝臟 LCATmRNA及ABCA1mRNA的表達量的情況。結果:①肝臟病理形態(tài)學改變:空白對照組肝臟組織結構未見異常,肝細胞以中央靜脈為中心呈放射狀,肝細胞的結構清晰,無脂肪變性的細胞;模型組大鼠可見肝細胞腫脹,伴有大量多余的脂肪滴存在;蘇木乙酸乙酯組大鼠肝臟可見輕度水腫,未見脂肪樣空泡形成;辛伐他汀組大鼠肝細胞腫脹減輕,并伴有水樣變性,偶可見極少量氣球樣變。②腹主動脈病理形態(tài)學改變:空白對照組腹主動脈血管壁內、中及外膜分界清楚;模型對照組血管內膜下可見平滑肌細胞排列紊亂、增生,同時可見極少量泡沫樣細胞的出現,彈力纖維層發(fā)生變性;蘇木乙酸乙酯組內皮細胞表面不光滑,少量平滑肌細胞排列紊亂、增生,中膜彈力纖維層排列不規(guī)則,外膜為纖薄的疏松結締組織;辛伐他汀組內膜下可見有少量炎性細胞及脂質沉積、平滑肌細胞增生且排列紊亂,并有排列不規(guī)則的中膜彈力纖維層出現,外膜變薄。③RT-PCR結果顯示:與空白組比較,各組肝臟組織中LCATmRNA表達顯著降低,差異具有統(tǒng)計學意義(P0.05);與模型組比較,蘇木乙酸乙酯提取物組及辛伐他汀組肝臟組織LCATmRNA的表達顯著升高,差異具有統(tǒng)計學意義(P0.05);蘇木乙酸乙酯提取物組與辛伐他汀組比較肝臟組織LCATmRNA表達量差異無統(tǒng)計學意義(P0.05)。④RT-PCR結果顯示:與空白組比較,各組肝臟組織中ABCA1 mRNA表達顯著降低,差異具有統(tǒng)計學意義(P0.05);與模型組比較,蘇木乙酸乙酯提取物組及辛伐他汀組肝臟中ABCA1mRNA的表達量顯著升高,差異具有統(tǒng)計學意義(P0.05);蘇木乙酸乙酯提取物組與辛伐他汀組比較肝臟中ABCA1mRNA表達差異無統(tǒng)計學意義(P0.05)。結論:1、蘇木乙酸乙酯提取物能夠減輕動脈粥樣硬化模型大鼠肝臟及腹主動脈病理形態(tài)學損傷。2、蘇木乙酸乙酯提取物能夠上調動脈粥樣硬化模型大鼠LCATmRNA、ABCA1mRNA 水平的表達。
[Abstract]:Aim: to observe the effect of pathological morphology of liver and abdominal aorta on the expression of pellucidylcholinesterase (LCAT) -ATP-binding cassette transporter A1 (ABCA1) in rat model of atherosclerosis. To explore the effect of ethyl acetate extract of sapphire on cholesterol reverse transport in atherosclerotic rats and the mechanism of ethyl acetate extract in preventing and treating atherosclerosis in order to provide experimental basis for clinical application of sappan. Methods: the atherosclerosis model of SD rats was induced by repeated injection of vitamin D 3.7 million IU (kg/d) and high fat diet. Forty adult rats were randomly divided into 4 groups: blank control group, model control group, ethyl acetate extract group and simvastatin group. The model of atherosclerosis was established by intraperitoneal injection of vitamin D 3.7 million IU (kg/d) for 3 days with the exception of blank control group, and fed with a high-fat diet for 12 weeks. After the model was successfully duplicated, each group was given continuously for 28 days. The histopathological changes of abdominal aorta and liver were observed by HE staining and the expression of LCATmRNA and ABCA1mRNA in liver by RealTime PCR. Results the pathomorphologic changes of the liver in the control group were as follows: there was no abnormal structure in the liver in the blank control group, the liver cells were radially centered on the central vein, the structure of the liver cells was clear, and there were no fatty degeneration cells in the model group, while in the model group, the liver cells were swollen. A large number of excess fat droplets were present in the liver of rats in the ethyl sappan acetate group, mild edema was observed in the liver, and no adipose vacuoles were found in the liver. In simvastatin group, the swelling of liver cells was alleviated and accompanied by watery degeneration. In the blank control group, the boundary between the medial and outer membranes of the abdominal aorta was clear, and the smooth muscle cells were arranged disorderly and proliferated under the intima of the model control group. At the same time, the appearance of a very small number of foam like cells, elastic fiber layer denaturation, hematoxylacetate ethyl acetate group endothelial cells surface is not smooth, a small number of smooth muscle cells arranged disorder, proliferation, media elastic fiber layer arranged irregularly, In simvastatin group, there were a few inflammatory cells and lipid deposition, smooth muscle cells proliferated and disordered, and irregular arrangement of elastic fiber layer appeared. The results of RT-PCR showed that compared with the blank group, the expression of LCATmRNA in liver tissue of each group was significantly decreased (P0.05); compared with the model group, the expression of LCATmRNA in the liver tissue of each group was significantly lower than that of the control group (P0.05). The expression of LCATmRNA in liver tissue of ethyl acetate extract group and simvastatin group was significantly higher than that of simvastatin group. Compared with simvastatin group, there was no significant difference in LCATmRNA expression in liver tissue between ethyl acetate extract group and simvastatin group (P0.05). 4 RT-PCR results showed: compared with the blank group, the expression of ABCA1 mRNA in liver tissue of each group was significantly lower than that of simvastatin group. The difference was statistically significant (P0.05). Compared with the model group, the expression of ABCA1mRNA in the liver of the ethyl acetate extract group and simvastatin group was significantly higher than that in the model group. The difference was statistically significant (P0.05); there was no significant difference in the expression of ABCA1mRNA between the ethyl acetate extract group and simvastatin group (P0.05). Conclusion the ethyl acetate extract of hematoxylum sappan can attenuate the pathomorphological damage of liver and abdominal aorta of atherosclerotic rats by 0.2, and the extract of ethyl acetate can up-regulate the expression of LCATmRNA,ABCA1mRNA in atherosclerotic rats.
【學位授予單位】：黑龍江中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R285.5;R-332

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