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目的探讨S-腺苷蛋氨酸(S-adenosylmethionine,SAM)对内毒素(lipolmlysaccharide,LPS)性肝损害的保护机制。方法 100只BABL/c小鼠随机数字法均分为2组,LPS组:腹腔注射10mg/kg的LPS;SAM组:在注射10mg/kgLPS前2h于小鼠腹腔内注射100mg/kg SAM。记录两组小鼠存活率;光镜和电镜观察组织病理学改变;酶联免疫吸附法(ELISA)检测血清中肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)的浓度;免疫组织化学法(SABC)和蛋白免疫印迹法(Western blot)检测肝组织中Toll样受体4(TLR4)和肝X受体α(LXRα)的蛋白表达水平。结果两组24、48、72、120h存活率比较,SAM组显著高于LPS组[(80.0%、70.0%、60.0%、50.0%)vs(50.0%、40.0%、30.0%、30.0%),P<0.05],肝脏病理损害程度减轻;SAM组血清中TNF-α水平显著低于LPS组,差异有统计学意义[(1791.79±122.19)pg/ml对(718.83±53.27)pg/ml,P<0.05];SAM组血清中IL-10增加且高峰前移,与LPS组比较差异有统计学意义[(418.69±38.77)pg/ml对(347.09±31.37)pg/ml,P<0.05];SAM组肝组织中LXRα表达明显增加,而TLR4表达则明显减少,两者与LPS组比较差异均有统计学意义{Western blot灰度值[TLR4:(1.550±0.034)对(1.365±0.017),LXRα:(1.605±0.027)对(1.375±0.014)],P<0.05}。结论 SAM能明显减轻LPS所致的肝损害,其机制可能与其降低肝脏各种细胞TLR4的表达,增强LXRα的表达,最终导致TNF-α水平降低和IL-10水平增高有关。
Objective To investigate the protective mechanism of S-adenosylmethionine (SAM) on hepatic injury induced by lipopolysaccharide (LPS). Methods 100 BABL / c mice were randomly divided into two groups. The LPS group was given intraperitoneal injection of LPS at 10 mg / kg. The SAM group was injected with 100 mg / kg SAM intraperitoneally at 2 h before injection of 10 mg / kg LPS. The survival rates of the two groups were recorded. The histopathological changes were observed under light microscope and electron microscope. The levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay (ELISA) . The protein expression of Toll-like receptor 4 (TLR4) and liver X receptor alpha (LXRα) in liver tissues were detected by immunohistochemistry (SABC) and Western blotting. Results The survival rates in the two groups were significantly higher than those in the LPS group at 24, 48, 72 and 120 h [(80.0%, 70.0%, 60.0%, 50.0%) vs (50.0%, 40.0%, 30.0%, 30.0% P <0.05]. The level of TNF-α in serum of SAM group was significantly lower than that of LPS group [(1791.79 ± 122.19) pg / ml vs (718.83 ± 53.27) pg / ml, P (P <0.05). Compared with LPS group, the level of IL-10 in serum of SAM group increased and reached its peak. [(418.69 ± 38.77) pg / ml vs 347.09 ± 31.37 pg / ml, P < Compared with LPS group, the expression of LXRα and the expression of TLR4 in the SAM group were significantly increased (P <0.05); the values of TLR4: (1.550 ± 0.034) vs (1.365 ± 0.017), LXRα: (1.605 ± 0.027) vs (1.375 ± 0.014)], P <0.05}. Conclusions SAM can reduce the hepatic damage induced by LPS obviously. Its mechanism may be related to the decrease of TLR4 expression and the expression of LXRα in various liver cells, leading to the decrease of TNF-α level and the increase of IL-10 level.