To Investigate The Effect Of Salidroside Combined With Dorsomorphin On Cerebral Ischemia-reperfusion Injury In Rats Based On The Gut Microbiota-Gut-brain Axis

Objective: To study the effect of Salidroside combined with Dorsomorphin on cerebral ischemia-reperfusion injury in rats and its mechanism based on the gut microbiota-brain-gut barrier pathway.Methods:1.After prophylactic intraperitoneal injection of Salidroside,Dorsomorphin,Salidroside + Dorsomorphin(50 mg/kg,20 mg/kg,50 + 20 mg/kg)dose solution for one week.The rat model of middle cerebral artery occlusion was established by suture method,and then the rats were given therapeutic administration for one week.To explore the effect of Salidroside combined with dorsomorphin on cerebral ischemia-reperfusion injury by neurological function score and TTC staining the area of cerebral infarction.2.The 16 S rRNA high-throughput sequencing technology was used to analyze the intestinal flora of rats.The synergistic effect of Salidroside combined with Dorsomorphin changed the composition of the intestinal flora and enriched the beneficial bacteria.Finally,colon and brain tissue were stained with HE,Real-time PCR was used to detect the expression of intestinal tight protein,and ELISA was used to detect intestinal flora shift indexes and inflammatory factors in plasma.To explore the effect of Salidroside combined with Dorsomorphin on cerebral ischemia-reperfusion injury in rats based on the gut microbiota-gut-brain axis.To explore the effect of Salidroside combined with Dorsomorphin on cerebral ischemia-reperfusion injury in rats based on the gut microbiota-gut-brain axis.Results:1.Prophylactic intraperitoneal injection,modeling,and then therapeutic administration for one week.Salidroside combined with Dorsomorphin can effectively improve neurological damage and reduce the area of cerebral infarction in rats.2.Cerebral ischemic stroke induces gut microbial disturbances by enriching pathogenic and opportunistic microorganisms,such as Proteobacteria and Enterobacteriaceae.However,Salidroside combined with Dorsomorphin remodeled the gut microbiome and improved gut microbial dysbiosis by modulating endogenous bacteria such as Ruminococcaceae,Oscillospira,Lachnospiraceae and Akkermansia.3.Cerebral ischemic stroke can also cause intestinal microbial translocation by increasing the permeability of the intestinal tract,destroying the intestinal and brain barrier.Salidroside combined with Dorsomorphin protects the brain-gut barrier by increasing claudin-5,occludin and ZO-1 m RNA levels;attenuates gut microbiota translocation by decreasing D-lactate,FABP,LPS,LBP,and DAO levels;and reduce systemic inflammatory response.Conclusion: The mechanism of Salidroside combined with Dorsomorphin against cerebral ischemia-perfusion injury may be related to its ability to effectively relieve intestinal microbial flora imbalance and gut-brain barrier damage.