基于免疫应激研究炮制对苍耳子致特异质肝损伤影响

Investigating Effect of Processing Cang'erzi(Xanthium sibiricum Patr.)on ldiosyncratic Drug-Induced Liver Injury Induced by Immunological Stress

目的探讨基于脂多糖(lipopolysaccharide,LPS)介导的免疫应激模型研究苍耳子(Xanthium sibiricum Patr.)经炮制后对特异性体质肝损伤的影响并初步探索其机制。方法采用SD大鼠尾静脉注射LPS方法构建免疫应激模型,实验分为正常组(Control)、生品组(raw products,RP)、炒品组(pan-fried products,FP)、酒品组(wine products,WP)、LPS组、生品低剂量联用LPS给药组(RPL+LPS)、生品高剂量联用LPS给药组(RPH+LPS)、炒品低剂量联用LPS给药组(FPL+LPS)、炒品高剂量联用LPS给药组(FPH+LPS)、酒品低剂量联用LPS给药组(WPL+LPS)、酒品高剂量联用LPS给药组(WPH+LPS)。检测分析血清谷丙转氨酶(Alanine aminotransferase,ALT)、天冬氨酸氨基转氨酶(Aspartat aminotransferase,AST)等肝功能指标、苏木素-伊红(Hematoxylin-eosin staining,HE)染色和原位末端转移酶标注技术(Terminal deoxynucleotidyl transferase dUTP nick end labeling,TUNEL)染色检测肝脏病理变化、血常规指标、血清细胞因子、炎症因子和氧化应激指标,对比考察苍耳子炮制前后单用或联合LPS的毒性差异。结果结果表明,苍耳子炒品、酒炙品能明显降低肝损伤大鼠血浆中ALT、AST等水平,减少大鼠肝组织炎症细胞浸润及肝细胞的凋亡,提示苍耳子炮制品具有抑制肝损伤的作用,而通过聚类图结果分析,苍耳子生品能导致特异性肝损伤;炒品苍耳子剂量低时对肝脏损伤小,剂量增加损伤加重,而酒品苍耳子对肝脏损伤较小。此外,苍耳子炒品、酒品可能通过降低炎症因子水平和降低白细胞、中性粒细胞、单核细胞的数目从而提高机体免疫状态、增强体内的抗氧化能力,恢复体内的氧化平衡,达到减轻特异质肝损伤的效果。结论机体在免疫应激的基础上,苍耳子生品能导致特异性肝损伤,经炒制、酒炙后的苍耳子减轻特异质性肝损伤,相比炒法而言,酒炙法减毒效果更为显著。

Objective To investigate the effect of processed Cang’erzi(Xanthium sibiricum Patr.)on specific liver injury caused by lipopolysaccharide(LPS)-mediated immune stress and explore its mechanism.Methods The immune stress model was established in SD rats by injecting LPS via the tail vein.The rats were divided into different groups,including a control group,raw products group(RP),pan-fried products group(FP),wine products group(WP),LPS group and various combina-tions of low and high dose raw,pan-fried and wine products with LPS(RPL+LPS,RPH+LPS,FPL+LPS,FPH+LPS,WPL+LPS,WPH+LPS)groups.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and other liver function in-dexes were detected.The liver pathological changes were observed by HE staining and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL staining).The blood routine indexes,serum cytokines,inflammatory factors and oxidative stress indexes were detected and analyzed.The the toxicity of Cang’erzi(Xanthium sibiricum Patr.)before and after processing with LPS alone or in combination was compared.Results The results showed that the fried and wine-processed products of Cang’erzi(Xanthium sibiricum Patr.)significantly reduced the levels of ALT and AST in plasma,reduced the infiltration of inflammatory cells in liver tissue,and decreased hepatocyte apoptosis in rats with liver injury.This suggests that the processed products of Cang’erzi(Xanthium sibiricum Patr.)could inhibit the liver injury.Cluster analysis indicated that Cang’erzi(Xanthium sibiri-cum Patr.)could cause specific liver injury.The severity of liver injury was lower with a low dosage of fried Cang’erzi(Xanthi-um sibiricum Patr.),but increased with a higher dosage.In contrast,the liver injury caused by wine-processed Cang’erzi(Xan-thium sibiricum Patr.)was minimal.Furthermore,the fried and wine products of Cang’erzi(Xanthium sibiricum Patr.)may im-prove the immune state of the body,enhance antioxidant capacity,restore oxidative balance,and reduce specific liver injury by re-ducing inflammatory factors and the number of white blood cells,neutrophils and monocytes.Conclusion Cang’erzi(Xanthium sibiricum Patr.)can cause specific liver injury in the raw state,but this injury is reduced after frying and wine processing.Wine processing has a more significant effect on reducing toxicity compared to frying.