温和灸对肛门瘙痒症脂质代谢网络的调控及皮肤微生态的影响

Mild moxibustion treatment of pruritus ani has advantages, Previous studies examined the itching models of TRPV1 expression in dorsal root ganglion cells in mice, made clear the activation of TRPV1 channels is one of the pathogenesis of pruritus ani, previous studies preliminarily the mild moxibustion could be related to the role of SAO is urticant symptom improvement model mice to warm stimulation vacuole reduce the skin cells. This study intends to surrounding mild moxibustion "warm stimulus - moxa smoke - lipid metabolic network changed biological signals - TRPV1 channels - skin micro ecological - anti-pruritic effect" this response process, to itch model mice as the carrier, with the help of 16 srrna high-throughput sequencing technologies and UPLC -ms technology, patch clamp whole cell recording technique, discussion crissum skin micro ecology and the incidence of anal pruritus, discusses the key metabolite of anal pruritus, explore the mild moxibustionmoxibustion mild moxibustion products regulatory mechanism of lipid metabolic network on the itching mice and skin micro ecological impact, for anal pruritus or other clinical TRP signaling pathways provide bioinformatics basis related diseases.

温和灸治疗肛门瘙痒症具有优势，前期的研究检测了瘙痒模型小鼠背根神经节细胞中TRPV1的表达，明确了TRPV1通路的激活是肛门瘙痒症的发病机制之一，初步明确了温和灸对瘙痒模型小鼠症状改善的作用可能与温热刺激减少皮肤细胞中液泡相关。本研究拟围绕温和灸“温热刺激-艾烟刺激-皮肤微生态-脂质代谢网络改变生物信号传递-TRPV1通路-止痒效应”这一应答过程，以瘙痒模型小鼠为载体，借助16SrRNA高通量测序法、UPLC-MS技术、膜片钳全细胞记录技术，探讨与肛门瘙痒症相关的肛周皮肤菌群及温和灸治疗对皮肤微生态的影响；寻找肛门瘙痒症的关键脂质代谢物；探讨温和灸的灸温和艾灸生成物对瘙痒小鼠脂质代谢网络的调控机制；明确温和灸对TRPV1通路的调节与改善瘙痒症状的关系。为临床上肛门瘙痒症或其他TRP信号通路相关的疾病提供生物信息学依据。

温和灸治疗肛门瘙痒症疗效显著，其作用机制尚不明确，本研究旨在探讨何种菌群导致肛门瘙痒，温和灸止痒效应是否与调节皮肤微生态相关，同时温和灸对肛门瘙痒症脂质代谢网络有何干预作用。基于16SrRNA的高通量测序分析肛门瘙痒小鼠与正常小鼠肛周皮肤微生态的差异，温和灸治疗后对各组小鼠肛周皮肤微生态的影响；基于UPLC-MS技术研究瘙痒小鼠与正常小鼠皮肤组织、血浆中脂质代谢物的差异；基于UPLC-MS技术研究艾灸生成物、不同灸温分别对瘙痒小鼠血浆、皮肤组织脂质代谢的干预。皮肤微生物组学发现Alpha多样性肛周瘙痒小鼠的Shannon指数和Simpson指数高于健康小鼠，温和灸治疗后肛周瘙痒小鼠的Shannon指数和Simpson指数明显降低。通过物种互作分析我们发现，相比于健康对照组，肛周瘙痒组和温和灸治疗组的互作网络更复杂，且负相互作用更多。脂质代谢结果提示PA小鼠存在血浆代谢紊乱，正常组、模型组之间存在15种脂质，温和灸38℃、46℃组均具有一定的回调作用，温和灸38℃组可回调4种脂质，温和灸46℃组可回调8种脂质，说明温和灸46℃组对PA模型小鼠的治疗效果较明显。艾烟组、无烟艾灸组对PA模型小鼠代谢紊乱同样有调节作用，艾烟组可回调13种脂质，无烟艾灸组可回调7种脂质，相较于无烟温和灸组，艾烟治疗对PA模型代谢产物回调更明显，说明艾烟组对PA治疗效果较明显。以上数据说明热和烟起到了是艾灸生成物中起效重要因素，而其中烟可能更为重要，而下一步艾烟通过何种方式参与调控代谢产物可能是下一步我们需要研究的重点。同时肛周瘙痒症与肛周皮肤微生物组中部分菌群的改变有关，温和灸治疗也会改变特定菌群的相对丰度，这对未来开发基于微生物制剂和温和灸的联合治疗方案具有重要的指导意义。