雷公藤红素的肝肾毒性分析及其对高脂饮食小鼠肠道菌群的调节作用

Liver and Kidney Toxicity of Celastrol and Its Regulating Action of Gut Microbiota on a High-fat Diet Mice

研究高脂饮食和雷公藤红素处理对小鼠肠道菌群及肝肾毒性的影响。用普通鼠粮和高脂鼠粮喂养小鼠,雷公藤红素高、中、低剂量组干预。高通量测序分析小鼠的肠道菌群,检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)活性及肌酐(Cr)、血尿素氮(Bun)含量。研究表明高脂饮食和雷公藤红素处理显著影响了小鼠肠道菌群构成,高脂饮食会显著降低小鼠肠道菌群的丰度和多样性,雷公藤红素处理可提高高脂饮食小鼠的肠道菌群的丰度和多样性,并且富集Ruminiclostridium和Anaerotruncus属菌,与对照组相比低、中、高剂量组Ruminiclostridium菌和Anaerotruncus菌含量分别增加51.26%、-44.62%、69.98%和62.45%、28.73%、17.86%。在100μg/kg^400μg/kg的雷公藤红素处理剂量下,AST、ALT活力值及Cr、Bun含量没有显著变化。说明高脂饮食和雷公藤红素处理显著影响了小鼠的肠道菌群结构,并且雷公藤红素在100μg/kg^400μg/kg的处理剂量下未见显著毒性。

The effects of a high-fat diet and celastrol treatment on gut microbiota and liver and kidney toxicity in mice were examined. Mice were fed a normal or high-fat rat diet, with a celastrol treatment at high, medium and low doses. High-throughput sequencing was used to analyze the intestinal flora of mice, and the activities of serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST), and the contents of creatinine(Cr) and blood urea nitrogen(Bun) were measured. Studies have shown that a high-fat diet and celastrol treatment significantly affect the composition of gut microbiota in mice. The high-fat diet reduced significantly the abundance and diversity of gut microbiota in mice. The celastrol treatment increased the abundance and diversity of gut microbiota in the mice fed the high-fat diet, while enriching the bacteria of the genus Ruminiclostridium and Anaerotruncus. Compared to the control group, the contents of Ruminiclostridium and Anaerotruncus in the low-, medium-and high-dose groups increased by 51.26%,-44.62% and 129.98%, and 62.45%, 28.73% and 17.86%, respectively. The treatment with celastrol at 100~400 μg/kg led to insignificant changes in the AST and ALT activities, and Cr and Bun contents. These results showed that the high-fat diet and celastrol treatment affected significantly the gut microbial structure of mice, and celastrol exhibited imsignificant toxicity at the treatment dose of 100~400 μg/kg.