滋阴和温阳方剂对帕金森病小鼠神经损伤及肠道炎症和肠微生态的影响

Effects of Zi Yin and Wen Yang Formulas on Nerve Damage and Intestinal Inflammation and Intestinal Microecology in Mice with Parkinson’s Disease

摘要: 目的：探索滋阴和温阳方剂(六味地黄丸与肾气丸)对帕金森病小鼠神经损伤及肠道炎症和肠微生态的影响。方法：将小鼠随机分为对照组、MPTP处理组、补脾组、滋阴组、温阳组，用MPTP诱导的亚急性帕金森病小鼠模型，观察滋阴和温阳方剂对帕金森病小鼠纹状体多巴胺含量、运动能力、回肠和纹状体中的细胞炎性因子的表达、肠道微生态的影响作用。结果：滋阴和温阳方剂可明显促进帕金森病小鼠神经损伤的恢复,促进多巴胺的含量增加(p < 0.05)，并且温阳方剂较滋阴方剂效果更明显(p < 0.05)，增加纹状体中酪氨酸羟化酶基因的表达(p < 0.05)，且温阳方剂效果更明显(p < 0.001)，运动能力较MPTP组也有显著的恢复(p < 0.05)并且温阳方剂较滋阴方剂效果更明显(p < 0.05)；抑制纹状体中IL-1β基因的表达(p < 0.05)，且温阳方剂效果更明显(p < 0.05)，抑制回肠中IL-1β基因的表达(p < 0.0001)，并促进回肠中IL-22基因的表达(p < 0.05)；促进回肠中的粘膜屏障结构修复；在门、科、属水平上，各组肠道微生物中优势物种类似，但丰度有所不同，滋阴组chao指数显著升高(p < 0.05)，PCoA分析中各组肠道微生物的群落组成均存在显著的差异(R = 0.2942, p =0.003)。讨论：滋阴方与温阳方(六味地黄丸与肾气丸)可以改善帕金森病小鼠所产生的运动症状、肠道菌群失调、肠道炎症、肠粘膜屏障受损、DA能神经细胞损伤的情况，且温阳配方较滋阴配方效果稍强。

Abstract: Objective: To explore the effects of Zi Yin and Wen Yang formulas (Liu Wei Di Huang Wan and Ren Qi Wan) on nerve injury and intestinal inflammation and intestinal microecology in mice with Parkinson’s disease. Methods: Mice were randomly divided into control group, MPTP-treated group, spleen tonic group, Zi yin group and Wen yang group with MPTP-induced subacute Parkinson’s disease mouse model to observe the effects of Zi Yin and Wen Yang formulas on striatal dopamine content, motility, expression of cellular inflammatory factors in ileum and striatum, and intestinal microecology in mice with Parkinson’s disease. Results: Zi Yin and Wen Yang formulas significantly promoted the recovery of nerve damage in Parkinson's disease mice, increased the content of dopamine (p < 0.05), and Wen Yang formulae were more effective than Zi Yin formulae (p < 0.05), increased the expression of tyrosine hydroxylase gene in the striatum (p < 0.05), and Wen Yang formulae were more effective (p < 0.001), and motor ability was also significantly restored compared with the MPTP group (p < 0.05). There was a significant recovery of motility (p < 0.05) and the effect of the Wen Yang formula was more pronounced than that of the Zi Yin formula (p < 0.05); inhibited the expression of IL-1β gene in the striatum (p < 0.05), and the effect of the Wen Yang formula was more pronounced (p < 0.05), inhibited the expression of IL-1β gene in the ileum (p < 0.0001), and promoted the expression of IL-22 gene in the ileum (p < 0.05); promoted the repair of mucosal barrier structure in ileum; at the level of phylum, family and genus, the dominant species were similar in each group of intestinal microorganisms, but the abundance was different, and the chao index was significantly higher in the Zi Yin group (p < 0.05), and there were significant differences in the community composition of intestinal microorganisms in each group in PCoA analysis (R = 0.2942, p = 0.003). Conclusion: The Zi Yin formula and the Wen Yang formula (Liu Wei Di Huang Wan and Ren Qi Wan) can improve the motor symptoms, intestinal flora dysbiosis, intestinal inflammation, intestinal mucosal barrier damage, and DAergic nerve cell damage produced by mice with Parkinson’s disease, and the Wen Yang formula is slightly more effective than the Zi Yin formula.