本文選題：急性肝衰竭 + 豬��； 參考：《鄭州大學》2007年碩士論文

【摘要】： 目的：以D-氨基半乳糖誘導建立急性肝衰竭動物模型，對其應用N-乙酰半胱氨酸(N-Acetylcysteine，NAC)治療，觀察NAC治療效果，深入研究藥物的作用機制。 方法：選用中國實驗小型豬，雌性，12頭，隨機分為兩組：對照組(n=6)與治療組(n=6)。應用D-氨基半乳糖1.2g/Kg靜脈注射誘導建立急性肝衰竭動物模型。治療組給藥后6小時、24小時、48小時分別給予NAC150mg/kg、50mg/kg、100mg/kg加入5％葡萄糖溶液100ml靜脈滴注，其后每間隔24小時給予NAC100mg/kg加入5％葡萄糖溶液100ml靜脈滴注。對照組給藥后6小時、24小時及其后每隔24小時分別靜脈滴注5％葡萄糖溶液100ml。觀察比較兩組動物一般狀況、生存時間、生理生化指標、顱內壓、組織病理變化及血清學相關因子變化。 結果：對照組動物平均存活時間為64.7±8.7小時，均死于嚴重肝衰竭。治療組存活時間為66.2±10.6小時，兩組平均存活時間比較，差異無顯著性意義(P=0.73，P＞0.05)。與對照組相比，治療組多項生化指標、顱內壓、炎性細胞因子等都有不同程度改善(p＜0.05～p＜0.01)。病理學檢查中治療組除60小時組外，其余時間點組織病理示較對照組有較好的恢復。免疫組化檢查中，對照組PCNA存在陽性表達，但數(shù)量較少，著色淺；治療組陽性表達數(shù)量多，著色相對較深。兩組陽性細胞計數(shù)后經(jīng)統(tǒng)計學分析，兩組陽性表達率的差異有顯著性意義(p＜0.05)；對照組和治療組中均有Caspase-3陽性表達，細胞質和細胞核均著棕黃色顆粒狀，疏密不等，但治療組的陽性顆粒數(shù)少于對照組。 結論：NAC應用于急性肝功衰竭治療具有一定的療效：①NAC治療可以改善機體的一般狀況和機能，在一定程度上為肝臟功能的恢復提供有益的幫助。②NAC治療可以減少體內TNF-a、IL-1β炎癥細胞因子的生成，抑制炎癥反應的快速發(fā)展，穩(wěn)定機體的內環(huán)境，減輕肝臟損傷，為肝細胞的再生、修復提供條件；③NAC治療對維持氧化和抗氧化的平衡發(fā)揮一定的作用，可以通過增加抗氧化劑SOD、還原性谷胱甘肽和一氧化氮的含量來清除肝臟內氧化劑產(chǎn)生的氧自由基，減少氧自由基對肝臟的損傷，，起到保護肝臟的作用；④NAC可以促進肝細胞的再生，有利于肝臟的功能恢復。綜上所述，N-乙酰半胱氨酸的應用為肝功能衰竭的臨床治療提供了一種有效的方法和新的選擇，具有重要的臨床意義。
[Abstract]:Aim: to establish an animal model of acute hepatic failure induced by D-galactosamine (D-galactosamine) and to observe the effect of N-Acetylcysteine NAC-1 (N-Acetylcysteine NAC-1) in the treatment of acute hepatic failure. Methods: twelve Chinese experimental miniature pigs were randomly divided into two groups: control group (n = 6) and treatment group (n = 6). Acute hepatic failure model was established by intravenous injection of D-galactosamine 1.2g/Kg. In the treatment group, NAC 150 mg 路kg ~ (-1) 50 mg 路kg ~ (-1) ~ (100 mg / kg) added 5% glucose solution (100ml) was given intravenously at 6 hours and 24 hours after administration respectively, and then NAC100mg/kg was injected intravenously with 5% glucose solution 100ml every 24 hours thereafter. In the control group, 5% glucose solution was injected intravenously for 24 hours 6 hours after administration and every 24 hours thereafter. The changes of general condition, survival time, physiological and biochemical indexes, intracranial pressure, histopathological changes and serological related factors were observed and compared between the two groups. Results: the average survival time of the control group was 64.7 鹵8.7 hours, all of them died of severe liver failure. The survival time of the treatment group was 66.2 鹵10.6 hours. There was no significant difference in the mean survival time between the two groups (P > 0.05). Compared with the control group, many biochemical indexes, intracranial pressure and inflammatory cytokines in the treatment group were improved to some extent (p < 0.05) and P < 0.01 (P < 0.01). In pathological examination, the histopathology of treatment group was better than that of control group except 60 hours group. In the immunohistochemical examination, the positive expression of PCNA was found in the control group, but the number was less and the staining was shallow, while in the treatment group, the number of positive expression was more and the staining was relatively deep. After counting the positive cells in the two groups, the difference of the positive expression rate between the two groups was significant (p < 0.05), the positive expression of Caspase-3 was found in both the control group and the treatment group, the cytoplasm and nucleus were brown granular, and the density was different. But the number of positive granules in the treatment group was less than that in the control group. Conclusion the application of WN NAC in the treatment of acute hepatic failure has a certain curative effect: 1 NAC can improve the general condition and function of the body. To a certain extent, NAC therapy can reduce the production of inflammatory cytokines, inhibit the rapid development of inflammatory response, stabilize the internal environment of the body, and alleviate liver injury. The treatment of NAC for the regeneration and repair of hepatocytes plays a certain role in maintaining the balance of oxidation and antioxidation. By increasing the contents of antioxidant SOD, reductive glutathione and nitric oxide, the oxygen free radicals produced by oxidants in the liver can be eliminated, the damage of oxygen free radicals to the liver can be reduced and the liver can be protected. 4NAC can promote the regeneration of hepatocytes and facilitate the recovery of liver function. To sum up, the application of N-acetylcysteine provides an effective method and a new choice for the clinical treatment of liver failure, and has important clinical significance.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2007
【分類號】：R575.3;R-332

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本文編號：1969109