辣木种子提取物对小鼠实验性肝损伤的保护作用
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摘要
目的考察辣木种子提取物对小鼠实验性肝损伤(急性酒精性肝损伤、四氯化碳致急性肝损伤)的保护作用。方法 RT-PCR、Western blotting分别检测小鼠肝组织ADH1和ALDH2 mRNA、蛋白表达。建立小鼠急性酒精性肝损伤模型,测定ALT、AST、ALP、LDH、GSH、MDA水平;建立小鼠四氯化碳致急性肝损伤模型,测定ALT、AST、GSH、MDA、T-SOD、GSH-Px、GR水平,RT-PCR检测C/EBPα、TNF-α、SREBP-1c、COX-2 mRNA表达,HE染色观察小鼠肝组织病理学变化。结果提取物(500 mg/kg)可提高ADH1 mRNA、蛋白表达,但对ALDH2无明显影响。对于急性酒精性肝损伤小鼠,各剂量提取物(125、250、500 mg/kg)降低ALT、AST、ALP、LDH、MDA水平,提高GSH水平;对于四氯化碳致急性肝损伤小鼠,各剂量提取物(32. 5、75、150 mg/kg)降低ALT、AST、MDA、GSHPx水平及COX-2、TNF-α、SREBP-1c mRNA表达,提高T-SOD、GSH、GR水平及C/EBPαmRNA表达,改善肝组织形态。结论辣木种子提取物对小鼠实验性肝损伤有明显保护作用,其机制可能与加快乙醇代谢、缓解炎症反应、抑制脂肪酸和胆固醇合成、改善脂质代谢紊乱有关。
AIM To investigate the protective effects of Moringa oleifera seed extract on experimental liver injury( acute alcoholic liver injury,carbon tetrachloride-induced acute liver injury). METHODS RT-PCR,Western blotting were applied to detecting the mRNA,protein expressions of ADH1 and ALDH2 in mouse liver tissue,respectively. The mouse models of acute alcoholic liver injury were established for the determination of ALT,AST,ALP,LDH,GSH,MDA levels; and the mouse models of carbon tetrachloride-induced acute liver injury were established for the detection of ALT,AST,T-SOD,MDA,GSH,GSH-Px,GR levels. RT-PCR for the mRNA expression detection of C/EBPα,TNF-α,SREBP-1c,COX-2,and HE staining for the observation of pathological changes of mouse liver tissue were performed. RESULTS The extract( 500 mg/kg) elevated ADH1 mRNA,protein expressions without obvious impact on those of ALDH2. Mouse models of acute alcoholic liver injury had reduced ALT,AST,MDA,GSH-Px levels and COX-2,TNF-α,SREBP-1c mRNA expressions,and elevated GSH level at various doses of the extracts( 125,250,500 mg/kg); mouse models of carbon tetrachloride-induced acute liver injury,shared reduced ALT,AST,MDA,GSH-Px levels and COX-2,TNF-α,SREBP-1c mRNA expressions,elevated T-SOD,GSH,GR levels and C/EBPα mRNA expression,and improved liver tissue morphology when applied with differently dosed extracts( 32. 5,75,150 mg/kg). CONCLUSION Moringa oleifera seed extract is obviously protective towards experimental mouse liver injury,whose mechanisms may contribute to accelerating ethanol metabolism,alleviating inflammatory reactions,inhibiting fatty acid and cholesterol synthesis,and improving lipid metabolism disorder.
AIM To investigate the protective effects of Moringa oleifera seed extract on experimental liver injury( acute alcoholic liver injury,carbon tetrachloride-induced acute liver injury). METHODS RT-PCR,Western blotting were applied to detecting the mRNA,protein expressions of ADH1 and ALDH2 in mouse liver tissue,respectively. The mouse models of acute alcoholic liver injury were established for the determination of ALT,AST,ALP,LDH,GSH,MDA levels; and the mouse models of carbon tetrachloride-induced acute liver injury were established for the detection of ALT,AST,T-SOD,MDA,GSH,GSH-Px,GR levels. RT-PCR for the mRNA expression detection of C/EBPα,TNF-α,SREBP-1c,COX-2,and HE staining for the observation of pathological changes of mouse liver tissue were performed. RESULTS The extract( 500 mg/kg) elevated ADH1 mRNA,protein expressions without obvious impact on those of ALDH2. Mouse models of acute alcoholic liver injury had reduced ALT,AST,MDA,GSH-Px levels and COX-2,TNF-α,SREBP-1c mRNA expressions,and elevated GSH level at various doses of the extracts( 125,250,500 mg/kg); mouse models of carbon tetrachloride-induced acute liver injury,shared reduced ALT,AST,MDA,GSH-Px levels and COX-2,TNF-α,SREBP-1c mRNA expressions,elevated T-SOD,GSH,GR levels and C/EBPα mRNA expression,and improved liver tissue morphology when applied with differently dosed extracts( 32. 5,75,150 mg/kg). CONCLUSION Moringa oleifera seed extract is obviously protective towards experimental mouse liver injury,whose mechanisms may contribute to accelerating ethanol metabolism,alleviating inflammatory reactions,inhibiting fatty acid and cholesterol synthesis,and improving lipid metabolism disorder.
引文
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[9] Weber L W,Boll M,Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes:carbon tetrachloride as a toxicological model[J]. Crit Rev Toxicol,2003,33(2):105-136.
[10] Shimizu I,Ma Y R,Mizobuchi Y,et al. Effects of Sho-saikoto,a Japanese herbal medicine,on hepatic fibrosis in rats[J].Hepatology,1999,29(1):149-160.
[11]于平.超氧化物歧化酶研究进展[J].生物学通报,2006,41(1):4-6.
[12] Huang G C,Zhang J S,Tang Q Q. Involvement of C/EBP-αgene in in vitro activation of rat hepatic stellate cells[J].Biochem Biophys Res Commun,2004,324(4):1309-1318.
[13] Horton J D,Goldstein J L,Brown M S. SREBPs:activators of the complete program of cholesterol and fatty acid synthesis in the liver[J]. J Clin Invest,2002,109(9):1125-1131.
[2] Rajanandh M G,Kavitha J. Quantitative estimation ofβ-sitosterol,total phenolic and flavonoid compounds in the leaves of Moringa oleifera[J]. Int J PharmTech Res, 2010, 2(2):1409-1414.
[3] Fakurazi S,Hairuszah I,Nanthini U. Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level[J]. Food Chem Toxicol, 2008, 46(8):2611-2615.
[4] Pari L, Kumar N A. Hepatoprotective activity of Moringa oleifera on antitubercular drug-induced liver damage in rats[J].J Med Food,2002,5(3):171-177.
[5] Chattopadhyay S,Maiti S,Maji G,et al. Protective role of Moringa oleifera(Sajina)seed on arsenic-induced hepatocellular degeneration in female albino rats[J]. Biol Trace Elem Res,2011,142(2):200-212.
[6] Donthamsetty S,Bhave V S,Mitra M S,et al. Nonalcoholic fatty liver sensitizes rats to carbon tetrachloride hepatotoxicity[J]. Hepatology,2007,45(2):391-403.
[7] Strubelt O,Younes M,Pentz R. Enhancement by glutathione depletion of ethanol-induced acute hepatotoxicity in vitro and in vivo[J]. Toxicology,1987,45(2):213-223.
[8] Vendemiale G,Altomare E,Grattagliano I,et al. Increased plasma levels of glutathione and malondialdehyde after acute ethanol ingestion in humans[J]. J Hepatol, 1989, 9(3):359-365.
[9] Weber L W,Boll M,Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes:carbon tetrachloride as a toxicological model[J]. Crit Rev Toxicol,2003,33(2):105-136.
[10] Shimizu I,Ma Y R,Mizobuchi Y,et al. Effects of Sho-saikoto,a Japanese herbal medicine,on hepatic fibrosis in rats[J].Hepatology,1999,29(1):149-160.
[11]于平.超氧化物歧化酶研究进展[J].生物学通报,2006,41(1):4-6.
[12] Huang G C,Zhang J S,Tang Q Q. Involvement of C/EBP-αgene in in vitro activation of rat hepatic stellate cells[J].Biochem Biophys Res Commun,2004,324(4):1309-1318.
[13] Horton J D,Goldstein J L,Brown M S. SREBPs:activators of the complete program of cholesterol and fatty acid synthesis in the liver[J]. J Clin Invest,2002,109(9):1125-1131.