氧化苦参碱对肝硬化大鼠肠源性内毒素血症的影响

Effect of Oxymatrine on Enterogenous Endotoxemia in Cirrhotic Rats

目的探究氧化苦参碱对肝硬化大鼠肠源性内毒素血症的影响。方法使用四氯化碳(CCl4)进行肝硬化大鼠模型制备,30只制备成功的肝硬化大鼠随机分成两组:治疗组接受氧化苦参碱肌内注射(63 mg·kg-1);模型组接受同等剂量5%葡萄糖溶液肌内注射。另取10只健康大鼠作为正常组。实验结束后,取大鼠门静脉血,使用鲎试剂盒,运用动态浊度法对血浆样品进行内毒素检测;取末段回肠组织,用ELISA试剂盒进行肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)浓度的测定,并进行光学显微镜下回肠组织病理学观察。结果模型组内毒素水平明显高于正常组,氧化苦参碱治疗后,治疗组内毒素水平明显下降,与模型组比较差异有统计学意义(P<0.01)。与模型组比较,治疗组回肠组织中TNF-α和IL-6的浓度显著下降(P<0.01)。模型组大鼠肠黏膜绒毛萎缩、脱落、断裂,黏膜固有层甚至肌层可见炎细胞浸润,绒毛水肿严重,并可见肌层组织水肿疏松;治疗组肠黏膜得到修复,绒毛整齐,水肿减轻,黏膜层致密,浸润的炎细胞明显减少。结论氧化苦参碱能降低肝硬化大鼠肠黏膜组织细胞因子TNF-α、IL-6的浓度水平,改善肠黏膜屏障功能,从而减轻肠源性内毒素血症。

Objective To investigate the effect of oxymatrine on enterogenous endotoxemia in rats with cirrhosis. Methods Thirty rats with carbon tetrachloride （CCl4 ）-induced cirrhosis were randomly divided into two groups：the treatmentgroup, who received oxymatrine intramuscular injection （63 mg·kg-1 ）;and the model control group, who received the samevolume of 5% glucose solution. Another 10 healthy rats served as the normal control group. At the end of the experiment, serumsamples were taken from the portal vein for the detection of endotoxin level with a Kinetic Turbidimetric Limulus AmebocyteLysate Kit. Concentration of TNF-αand IL-6 in the ileum tissue was analyzed by enzyme-linked immunosorbent assay （ELISA）.A piece of terminal ileum was also sampled for histopathologic examination. Results The serum endotoxin level wassignificantly elevated in the model control group than the normal control group. After the treatment with oxymatrine, the serumendotoxin level was significantly decreased compared with the model control （P〈0. 01）. Administration of oxymatrine resulted ina significant reduction in the concentration of TNF-αand IL-6 compared with the model control group （P〈0. 01）. The intestinalmucosal villi in rats of the model control group were atrophic, shorter, fractured, and infiltrated with inflammatory cells into thelamina propria and even muscular layer. The swelling of the villi was serious and structure of mucous membrane became loose.This observation was reversed in the treatment group. Conclusion Oxymatrine decreased enterogenous endotoxemia incirrhotic rats by reducing the concentration of TNF-αand IL-6 and improving intestinal barrier function.