基于相关可视化的壮骨关节丸特异质肝损伤与27种细胞因子的相关性分析

Correlation analysis on idiosyncratic hepatotoxicity of Zhuangguguanjie Wan and 27 cytokines based on related visualization

目的采用相关可视化的方法,探讨壮骨关节丸(Zhuangguguanjie Wan,ZGW)特异质肝损伤指标丙氨酸转氨酶(ALT)与27种细胞因子的相关性。方法 SD大鼠禁食12 h后,ig给予ZGW 3.8 g/kg,2 h后尾iv 2.8 mg/kg的脂多糖(LPS),给予LPS 10 h后水合氯醛麻醉大鼠,下腔静脉取血,采集肝组织样本。检测血清中ALT活力及肝脏组织27种细胞因子水平。R 3.2.4软件分析ALT与27种细胞因子及27种细胞因子之间的相关性。结果 ALT与巨噬细胞炎性蛋白1α(MIP-lα)和血管内皮生长因子(VEGF)之间具有较强的正相关性,白细胞介素-18(IL-18)、趋化因子-10(IP-10)、IL-1α和IL-1β之间具有很强的相关性,嗜酸性粒细胞趋化因子(eotaxin)或调节活化正常T细胞表达和分泌的趋化因子(RANTES)各自具有独立性。结论 ZGW特异质肝损伤与MIP-1α和VEGF之间具有较强的正相关性,为ZGW临床安全用药及风险防控提供新的实验证据。

Objective To analyze the correlation of idiosyncratic hepatotoxicity of Zhuangguguanjie Wan（ZGW） with 27 cytokines. Methods After 12 h fasting, SD rats were ig with ZGW at a single dose of 3.8 g/kg, and injected with lipopolysaccharide（LPS） at a dosage of 2.8 mg/kg via tail vein after 2 h. The rats were anesthetized with chloral hydrate after 10 h LPS administration, and then the blood samples were collected from the inferior vena cava and liver tissue was also obtained. Alanine aminotransferase（ALT） activity in serum and levels of 27 cytokines in liver tissue were tested. Correlation analysis of ALT and cytokines were performed using R 3.2.4 software. Results Correlation analysis showed that there was a high positive correlation between ALT and macrophage inflammatory protein-1α（MIP-1α） or vascular endothelial growth factor（VEGF）. There was a strong correlation among interleukin-18（IL-18）, interferon-inducible protein-10（IP-10）, interleukin-1α（IL-1α）, and interleukin-1β（IL-1β）. However, eotaxin regulated upon activation of normal T cell expression and secreted factor（RANTES）, which has their own independence. Conclusion Idiosyncratic liver injury induced by ZGW has a strong positive correlation with MIP-1α and VEGF, which provides a new experimental evidence for clinical medication safety and risk prevention of ZGW.