三硫二丙烯调节免疫因子保护异烟肼和利福平联合引起的小鼠肝损伤

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目的探讨三硫二丙烯(Diallyltrisulfide,DATS)对异烟肼(Isonicotinic acid hydrazide,INH)和利福平(Rifampicin,RFP)联合用药所导致小鼠肝损伤的保护效果评价及其可能的机制。方法将96只雄性昆明小鼠完全随机分空白对照组、DATS对照组、INH+RFP处理组和DATS低、中、高剂量联合处理组,每组16只。DATS低、中、高联合处理组及DATS对照组分别给予10、20、40和40 mg/kg的DATS,空白对照组和INH+RFP处理组给予等体积的玉米油;2 h后给予INH+RFP处理组及DATS低、中、高联合处理组INH(150 mg/kg)和RFP(100 mg/kg),空白对照组和DATS对照组给予等体积的生理盐水。连续灌胃11 d后处死,测定小鼠肝脏重量及肝/体比值、血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(T-BIL)、γ-谷氨酰基转移酶(GGT)的水平;肝组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1-β(Interleukin 1-β,IL-1-β)和肝脏组织病理检查。结果与空白对照组比较,INH+RFP处理组出现了明显的体重下降(P<0.01);肝/体比值升高(P<0.01);ALT、AST、T-BIL和ALT/GGT水平升高(PALT、T-BIL、GGT<0.01,PAST<0.05);肝脏病理切片显示,INH+RFP处理组肝内细胞排列不规则,出现大量的空泡及细胞坏死,肝细胞核变大深染,DATS组明显减少;肝组织匀浆中模型组TNF-α水平显著增高(P<0.01),IL-1-β水平降低(P<0.01);DATS低、中、高浓度联合处理组各指标出现明显好转,且DATS高剂量联合处理组保护效果最好,与正常对照组没有明显的差别。保护作用呈一定的剂量-反应关系。结论三硫二丙烯能抑制异烟肼和利福平所致的小鼠肝损伤,其机制与调节肝组织内免疫因子的分泌有关。 Objective To investigate the protective effect of Diallylisiside (DATS) on hepatic injury in mice induced by combination of Isonicotinic acid hydrazide (INH) and Rifampicin (RFP) and its possible mechanism. Methods Ninety-six male Kunming mice were randomly divided into blank control group, DATS control group, INH + RFP treatment group and DATS low, medium and high dose combination treatment group, 16 rats in each group. DATS low, medium and high combined treatment group and DATS control group were given 10,20,40 and 40 mg / kg of DATS, blank control group and INH RFP group were given an equal volume of corn oil; 2 h after INH + RFP group and DATS low, medium and high combined treatment group INH (150 mg / kg) and RFP (100 mg / kg), blank control group and DATS control group were given equal volume of saline. The mice were sacrificed on the 11th day after continuous gavage. The liver weight, liver / body ratio, serum ALT, AST, T-BIL, (GGT), and the level of Interleukin 1-β (IL-1β) and liver histopathological examination in liver tissue. Results Compared with the blank control group, the weight loss of INH + RFP group was significant (P <0.01); the ratio of liver / body was increased (P <0.01); the levels of ALT, AST, T-BIL and ALT / GGT were increased (PALT, T-BIL, GGT <0.01, PAST <0.05). Liver pathological sections showed irregular arrangement of intrahepatic cells in INH + RFP group with a large number of vacuoles and necrosis, (P <0.01), while the level of IL-1-β was decreased (P <0.01). The indexes of low, middle and high concentration of DATS group were obvious Improved, and DATS high-dose combination treatment group the best protective effect, and the normal control group no significant difference. Protective effect was dose-response relationship. Conclusion Thioxins and rifampin-induced liver damage in mice can be inhibited by trithio-diprolol. The mechanism is related to the regulation of the secretion of immune factors in liver tissues.
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