基于“二阳为卫”理论探讨补肾填精方防治老年骨质疏松症肠稳态失衡的机制研究

Neijing two Yang disease theory suggests that Yangming disease can cause Guwei; Neijing two Yang Wei and Wei Qi is riddled with mother theory suggests that Yang Ming Wei Qi weak and intestinal immune homeostasis are closely related, in-depth scrutiny of Yang Ming Wei Qi has important clinical the guidance significance for prevention and treatment of senile osteoporosis; Neijing Wei from the lower Jiao and Wei aerial roots in the kidney theory suggests that kidney tonifying Yangming to benefit the recovery of intestinal homeostasis is effective treatment; Zhang Jingyue's Qi is Yang, Yang will be born in Yin, fine Yin also prompt theory although Wei Yang from Yin and rule, when. Effect of kidney tonifying recipe of Zuogui pill can kidney tonifying Yangming to benefit, thus effectively preventing and treating senile osteoporosis mice (SAMP6), and its regulating intestinal homeostasis induced by aging related, affect the intestinal microbial ecosystem, protecting intestinal mucosal barrier, start maintaining immune response of intestinal homeostasis and osteoclast; mechanism of action the influence of precursor cells by RAW264.7 CX3CR1/CX3CL1 axis intervention to regulate between macrophages and osteoclasts role homeostasis.

《内经》“二阳之病”理论提示阳明病变可致“骨痿”；《内经》“二阳为卫”和“卫气为百病母”理论提示“阳明卫气弱”与“肠免疫稳态失衡”密切相关，深入审察阳明卫气对防治老年骨质疏松症具有重要临床指导意义；《内经》“卫出于下焦”和“卫气根于肾”理论提示“补肾填精”以益阳明是恢复肠稳态的有效治法；张景岳之“气为阳也，阳必生于阴，精为阴也”理论提示卫虽为阳，当从阴而治。补肾填精方左归丸能够“补肾填精”以益阳明，从而有效防治老年性骨质疏松症模型小鼠（SAMP6），与其调节衰老所致肠稳态失衡有关，影响肠道微生物生态系统，保护肠黏膜屏障，启动维持肠道内稳态的免疫应答；作用机制与通过影响破骨细胞的前体单核细胞RAW264.7干预CX3CR1/CX3CL1轴以调节巨噬细胞和破骨细胞之间的作用稳态有关。

衰老导致的慢性疾病成为研究热点，衰老致骨代谢异常，发生肠黏膜屏障损伤和骨质疏松等形质损伤。基于二阳为卫，卫出下焦，从阴治形。探讨补肾填精方对老年骨质疏松治疗作用是否与其影响肠稳态有关，肠道菌群失调是否与免疫低下和炎症损害相关。选用快速老化骨质疏松模型小鼠SAMP6，采用电镜和Micro-CT观察组织微结构，Western blot检测骨功能、炎症因子和肠紧密连接蛋白。16S测序，进行粪便肠道菌群构成、多样性、相关性分析。RANKL诱导单核巨噬细胞RAW264.7建立破骨细胞模型，采用MTT法检测细胞存活率，ELISA和Western blot检测IL-17和IL-10。补肾填精方改善骨和肠组织形态及微结构，上调骨和肠ALP、肠ZO-1蛋白、血清IgG和IL-10，下调肠IL-17。在属分类水平，与SAMR1比较，SAMP6小鼠Prevotellaceae_UCG-001和Akkermansia升高，Desulfovibrio降低。补肾填精方可以逆向调节。Prevotellaceae_UCG-001与IL-17呈正相关，Prevotellaceae_UCG-001、Akkermansia与IgG呈负相关。补肾填精方组破骨细胞增殖率降低，IL-17降低。补肾填精方可以上调IL-10，补肾填精方+ICI182 780组下调IL-10。SAMP6小鼠肠道菌群出现明显变化，肠黏膜屏障损伤，肠道菌群失调与免疫低下和炎症损害发生相关，肠道菌群在维持骨骼健康和免疫稳态中发挥着重要作用。补肾填精方有抗骨质疏松作用，调节肠道菌群，改善肠黏膜屏障，影响免疫功能和炎症因子水平。对骨和肠道菌群的深入研究，将会为骨质疏松症的诊断和治疗开辟出一条新的途径。被补肾填精方调节肠道菌群可能是该药物防治衰老所致骨质疏松症的潜在作用靶点，为发现补肾填精方潜在的抗骨质疏松症作用靶点提供了新的研究思路。