[Study on protective effect and mechanism of Shouhui Tongbian Capsules on cerebral ischemia-reperfusion rat models based on metabolomics].

This paper explored the protective effect and potential mechanism of Shouhui Tongbian Capsules(SHTB) on cerebral ischemia-reperfusion rat models. Rats were randomly divided into sham surgery group, model group, low-dose SHTB group(0.2 g·kg~(-1)·d~(-1)), high-dose SHTB group(SHTB g·kg~(-1)·d~(-1)), and an edaravone positive drug group(5.4 mg·kg~(-1)·d~(-1)), with 12 rats in each group. Rats were given continuous intragastric administration seven days before surgery, and the suture method was used to establish the cerebral ischemia-reperfusion injury(CIRI) rat model. Zea-Longa rating scale for neurological functions was used to assess the degree of neurological function impairment in rats; hematoxylin-eosin(HE) staining was used to observe the pathological damage of rats' brain tissue; TTC staining was used to measure the area of cerebral infarction in rats; enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in each group. Western blot was used to detect the level of tight junction protein associated with the blood-brain barrier and intestinal barrier, as well as the protein expression of the TLR4/MyD88/NF-κB pathway in brain tissue. Changes in rats' brain tissue and metabolites in serum were detected by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS), so as to explore the potential mechanism of SHTB treatment for CIRI in rats. Compared with the model group, SHTB could significantly alleviate the pathological damage to the brain of CIRI rats, reduce the volume of cerebral infarction, and lower the level of inflammation in the serum; Western blot results showed that SHTB could regulate the expression of tight junction proteins related to the blood-brain barrier and intestinal barrier in CIRI rats and downregulate the expression of TLR4, NF-κB, and MyD88 proteins in brain tissue. The UPLC-MS/MS results indicated that SHTB could significantly regulate the content of potential differential metabolites such as fatty acids, and serum and brain tissue are involved in pathways such as unsaturated fatty acid biosynthesis. SHTB could repair intestinal barrier function, reduce inflammation levels in the body, and improve the damaged blood-brain barrier, exerting a protective effect on brain nerves. Its mechanism may be achieved by balancing fatty acid metabolism and regulating the expression of TLR4/MyD88/NF-κB signaling pathway proteins.