Department of Integrated Traditional and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
CNS Neurosci Ther. 2023 Jun;29 Suppl 1(Suppl 1):161-184. doi: 10.1111/cns.14247. Epub 2023 May 8.
Gastrointestinal (GI) dysfunction, as a common peripheral-organ complication after traumatic brain injury (TBI), is primarily characterized by gut inflammation and damage to the intestinal mucosal barrier (IMB). Previous studies have confirmed that TongQiao HuoXue Decoction (TQHXD) has strong anti-inflammatory properties and protects against gut injury. However, few have reported on the therapeutic effects of TQHXD in a TBI-induced GI dysfunction model. We aimed to explore the effects of TQHXD on TBI-induced GI dysfunction and the underlying mechanism thereof.
We assessed the protective effects and possible mechanism of TQHXD in treating TBI-induced GI dysfunction via gene engineering, histological staining, immunofluorescence (IF), 16S ribosomal ribonucleic acid (rRNA) sequencing, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and flow cytometry (FCM).
TQHXD administration ameliorated TBI-induced GI dysfunction by modulating the abundance and structure of bacteria; reconstructing the destroyed epithelial and chemical barriers of the IMB; and improving M1/M2 macrophage, T-regulatory cell (Treg)/T helper 1 cell (Th ), as well as Th /Treg ratios to preserve homeostasis of the intestinal immune barrier. Notably, Cluster of Differentiation 36 (CD36)/15-lipoxygenase (15-LO)/nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling was markedly stimulated in colonic tissue of TQHXD-treated mice. However, insufficiency of both CD36 and (C-X3-C motif) chemokine receptor 1 (CX3CR1) worsened GI dysfunction induced by TBI, which could not be rescued by TQHXD.
TQHXD exerted therapeutic effects on TBI-induced GI dysfunction by regulating the intestinal biological, chemical, epithelial, and immune barriers of the IMB, and this effect resulted from the stimulation of CD36/NR4A1/15-LO signaling; however, it could not do so when CX3CR1 and CD36 were deficient. TQHXD might therefore be a potential drug candidate for treating TBI-induced GI dysfunction.
胃肠道（GI）功能障碍是创伤性脑损伤（TBI）后常见的外周器官并发症，其主要特征为肠道炎症和肠黏膜屏障（IMB）损伤。既往研究证实，通窍活血汤（TQHXD）具有较强的抗炎作用，并可预防肠道损伤。然而，很少有研究报道 TQHXD 在 TBI 诱导的 GI 功能障碍模型中的治疗效果。本研究旨在探讨 TQHXD 对 TBI 诱导的 GI 功能障碍的治疗作用及其潜在机制。
我们通过基因工程、组织学染色、免疫荧光（IF）、16S 核糖体核糖核酸（rRNA）测序、实时聚合酶链反应（RT-PCR）、酶联免疫吸附测定（ELISA）、Western blot（WB）和流式细胞术（FCM）评估 TQHXD 治疗 TBI 诱导的 GI 功能障碍的保护作用及其可能的机制。
TQHXD 通过调节细菌的丰度和结构、重建 IMB 破坏的上皮和化学屏障、改善 M1/M2 巨噬细胞、T 调节细胞（Treg）/辅助性 T 细胞 1（Th1）以及 Th1/Treg 比值，从而改善 TBI 诱导的 GI 功能障碍。值得注意的是，TQHXD 治疗的小鼠结肠组织中 CD36/15-脂氧合酶（15-LO）/核受体亚家族 4 组 A 成员 1（NR4A1）信号明显增强。然而，CD36 和（C-X3-C 基序）趋化因子受体 1（CX3CR1）的不足会加重 TBI 诱导的 GI 功能障碍，而 TQHXD 对此无改善作用。
TQHXD 通过调节 IMB 的肠道生物学、化学、上皮和免疫屏障对 TBI 诱导的 GI 功能障碍发挥治疗作用，这一作用源于 CD36/NR4A1/15-LO 信号的刺激；然而，当 CX3CR1 和 CD36 缺乏时，这种作用则无法实现。因此，TQHXD 可能是治疗 TBI 诱导的 GI 功能障碍的潜在药物候选物。
