丹参多酚酸盐对急性肝衰竭大鼠的早期治疗作用研究

Early protective effect of salvianolic acid A on acute hepatic failure in rats

目的研究丹参多酚酸盐对急性肝衰竭大鼠早期治疗效果并探讨其中可能的机制。方法建立D-氨基半乳糖（D-gag actosamine，D～GaIN）和脂多糖（LPS）诱导的大鼠急性肝衰竭模型，观察早期应用丹参多酚酸盐对大鼠存活率和肝组织病理改变的影响，以及对肝功能指标（ALT、AST、TB）的影响和肿瘤坏死因子-α（TNF—α）、白细胞介素-6（IL-6）的调节。结果早期使用丹参多酚酸盐组（给药组）死亡比例为5／12，未给药组（AHF组）死亡比例为10／12，两组死亡率比较差异有统计学意义（P〈0．05）。肝组织病理学镜检显示，给药组肝组织结构基本完整，可见肝细胞肿胀，部分细胞空泡变性，并见碎片状坏死，少量充血和少量炎细胞浸润；AHF组见肝小叶结构破坏，肝细胞大片变性坏死，坏死区炎细胞浸润，肝窦扩张，可见淤血及出血，给药组病理形态学明显改善。给药组病理指数为0．19±0．10，AHF组为0．34±0．09，两组比较差异有统计学意义（P〈0．05）。给药组ALT、AST和TB分别为（1593±706）U／L、（2978±521）U／L和（7．18±2．98）μmol／L，AHF组分别为（4973±1582）U／L、（5498±2730）U／L和（16．37±2．45）μmol／L，两组比较差异有统计学意义。蛋白免疫印迹法显示，给药组肝组织TNF-α和IL-6表达下调。结论使用丹参多酚酸盐对急性肝衰竭大鼠具有明显的治疗效果，其机制可能涉及下调促炎细胞因子TNF-α和IL-6的表达。

Objective To observe the early protective effect of salvianolic acid A on acute hepatic failure in rats. Methods Rats models of acute hepatic failure were established by the injection old-gag actosamine（D- GAIN） and lipopolysaccharide （LPS） intraperitoneally, and the liver injury and mortality of rats were detected. The level of ALT, AST, TB in serum and the expression of TNF - α or IL -6 in hepatic tissues were determined. Results Mortality rate in the group administrated with salvianolic acid A was 5/12, and was 10/12 in untreated group. Pathology microscopy of liver tissue was performed. General integrity of the structure of the liver tissue was seen in the group treated with salvianolic acid A, including vacuolar degeneration, piecemeal necrosis partially and few inflammatory cells infiltration. Hepatic lobule structural damage was detected in untreated group, with large areas of degeneration and necrosis of liver cells, inflammation cells infiltration, congestion and bleeding in sinusoidal areas. Pathological index of the treated group or untreated group was 0.19 ± 0.10 or 0.34 ± 0.09. Three liver function indicators of ALT, AST, TB were （ 1593 ± 706） U/L, （2978 ± 521 ） U/L, （7.18 ±2.98） μmol/L in treated group, and （4973 ± 1582） U/L, （5498 ± 2730） U/L, （ 16.37 ± 2.45 ） μ mol/L in untreated group, which indicated an improvement of liver function after administration of salvianolic acid A. The expressions of TNF - α and IL - 6 in hepatic tissue were determined by Western - blotting and a down - regulation of them was found. Conclusion Early administration of salvianolic acid A can protect rats against acute hepatic failure with an underlying relationship of the down - regulation of pro - inflammation cytokines TNF - α and IL - 6.