Zhai Yang, Luo Yihui, Mo Xueni, Yang Peng, Pang Yan, Wu Lin, Zheng Guangshan, Zou Min, Ma Wei, Wang Kaihua, Li Yan, Chen Ying, Mei Xiaoping
Department of International Medical, Guangxi International Zhuang Medicine Hospital, Nanning, China.
Department of Neurology, Guangxi University of Chinese Medicine, Nanning, China.
Ann Transl Med. 2023 Feb 28;11(4):174. doi: 10.21037/atm-23-253.
The standardized treatment of ischemic stroke (IS) with Shuanglu Tongnao Compound Recipe (SLTNCR) combined with Western medicine has improved the life quality and neurological function of patients and achieved a satisfactory clinical effect. However, the underlying mechanisms of SLTNCR in the treatment of IS remain unclear.
A rat model of IS was prepared using Longa's wire bolus method. SLTNCR was administered by gavage with following doses: low dose, 7.16 g·kg; middle dose, 14.33 g·kg; high dose, 28.66 g·kg. The expressions of toll-like receptor 4 (TLR4), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, nuclear factor-κB (NF-κB), etc., brain neuron damage, small intestine structure, and the structure of intestinal flora of rats in the high, medium, and low dose SLTNCR groups as well as the Injury + Clostridium butyricum and Injury + Edaravone groups were detected by 16SrRNA gene sequencing, western blot, hematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR).
SLTNCR significantly reduced the brain water content, decreased the cerebral infarct size, and improved the neurological deficits, neuronal damage, small bowel tissue damage, and expression of inflammatory factors [B-cell CLL/lymphoma 2 (Bcl-2), BCL2 associated agonist of cell death (Bad), cleaved-caspase-3] in brain tissue. SLTNCR administration significantly inhibited expressions of TLR4, NF-κB, and inhibitor of nuclear factor kappa B (IκB), and decreased phosphorylation levels of NF-κB and IκB in the small intestinal tissues of IS rats. Moreover, SLTNCR also significantly upregulated the expression of intestinal barrier function-related molecules [zona occludens 1 (ZO-1), occludin, claudin-5] and regulated the expression of colonic TLR4, TNF-α, IL-6, and IL-1β. SLTNCR can improve the symptoms of IS rats by improving brain and small intestinal function, particularly by regulating the TLR4/NF-κB signaling pathway, apoptotic proteins, and inflammatory factors in brain tissue. Gut microbiota analysis helped to identify the pharmacological mechanisms underlying the effects of SLTNCR on intestinal bacterial diversity and flora structure in IS rats.
SLTNCR can alleviate symptoms of IS and the potential mechanism of its effect is to protect brain tissue by suppressing inflammation. SLTNCR can also alter the structure and diversity of the bacterial community in IS.
双路通脑复方制剂（SLTNCR）联合西药对缺血性脑卒中（IS）进行标准化治疗，提高了患者的生活质量和神经功能，取得了满意的临床效果。然而，SLTNCR治疗IS的潜在机制仍不清楚。
采用Longa线栓法制备IS大鼠模型。通过灌胃给予SLTNCR，剂量如下：低剂量，7.16 g·kg；中剂量，14.33 g·kg；高剂量，28.66 g·kg。采用16SrRNA基因测序、蛋白质免疫印迹法、苏木精-伊红（HE）染色、酶联免疫吸附测定（ELISA）和聚合酶链反应（PCR）检测高、中、低剂量SLTNCR组以及损伤+丁酸梭菌组和损伤+依达拉奉组大鼠的Toll样受体4（TLR4）、肿瘤坏死因子（TNF-α）、白细胞介素-1β（IL-1β）、IL-6、核因子-κB（NF-κB）等的表达、脑神经元损伤、小肠结构和肠道菌群结构。
SLTNCR显著降低脑含水量，减小脑梗死体积，改善神经功能缺损、神经元损伤、小肠组织损伤以及脑组织中炎症因子[B细胞淋巴瘤/白血病-2（Bcl-2）、细胞死亡相关的BCL2激动剂（Bad）、裂解的半胱天冬酶-3]的表达。给予SLTNCR显著抑制IS大鼠小肠组织中TLR4、NF-κB和核因子κB抑制因子（IκB）的表达，并降低NF-κB和IκB的磷酸化水平。此外，SLTNCR还显著上调肠道屏障功能相关分子[紧密连接蛋白1（ZO-1）、闭合蛋白、Claudin-5]的表达，并调节结肠TLR4、TNF-α、IL-6和IL-1β的表达。SLTNCR可通过改善脑和小肠功能，特别是通过调节脑组织中的TLR4/NF-κB信号通路、凋亡蛋白和炎症因子来改善IS大鼠的症状。肠道微生物群分析有助于确定SLTNCR对IS大鼠肠道细菌多样性和菌群结构影响的药理机制。
SLTNCR可缓解IS症状，其作用的潜在机制是通过抑制炎症来保护脑组织。SLTNCR还可改变IS中细菌群落的结构和多样性。
