Effect And Mechanism Of Shengmakainao Decoction On Ameliorating Brain Injury Of Vascular Dementia Rats

Objective:To investigate the effect and mechanism of Shengma Kainao Decoction on cerebral injury of vascular dementia rats.Methods: After 7 days of adaptive feeding,50 SPF adult male SD rats were randomly divided into 5 groups,namely the sham-operation group,the model group,the low-dose Shengmakainao Decoction group,and the high-dose Shengmakainao Decoction group and donepezil hydrochloride group.Shengmakainao Decoction was prepared by soaking,decocting,filtering and concentrating the traditional Chinese medicinal materials.Except for the sham-operated group,the other groups were used "permanent bilateral common carotid artery occlusion + sodium nitroprusside hypotensive method" to establish the VD rat model.On the day 7 after the modeling operation,the Shengmakainao Decoction low-dose group was given 0.45 g/kg·d Shengmakainao Decoction solution,and the Shengmakainao Decoction high-dose group was given 1.8 g/kg·d Shengmakainao Decoction solution,the donepezil hydrochloride group was given 0.512 mg/kg·d,the model group and the sham-operated group were given the same volume of normal saline,and the experimental groups were given 28 d by gavage.During the test period,the health status of the rats in each group was observed.At the end of the test period,the body weight of the rats in each group was weighed.The learning and memory ability of rats was detected by the Morris water maze positioning navigation test.The activities of acetylcholinesterase(AchE)and serotonin(5-HT)in rat serum were determined by detection kit and ELISA.Histopathological changes of rat hippocampus were observed by HE staining.The serum levels of inflammatory factors TNF-α,IL-6 and IL-1β were detected by ELISA,and the expressions of TLR4 and NF-κB signaling pathway key protein NF-κB in brain tissue were detected by Western blot method.The apoptosis of hippocampal cells was detected by TUNEL method,and the expressions of apoptosis-related proteins Bax,Bcl-2 and Cleaved-caspase3 in brain tissue were detected by Western blot method.Results: The results of body weight statistics showed that VD rats did not cause changes in their body weight during the test,and low-dose Shengmakainao Decoction,high-dose Shengmakainao Decoction,and donepezil hydrochloride did not cause changes in body weight in VD rats.Morris The results of the water maze positioning navigation test showed that the VD rats were successfully modeled,and the VD rats in the high-dose Shengmakainao Decoction group had a significantly shorter latency period,which was better than that in the Shengmakainao Decoction low-dose group,and was comparable to the donepezil hydrochloride group.The AchE activity assay results showed that the AchE activity in the serum of the VD rats in the low-dose Shengmakainao Decoction group,the high-dose Shengmakainao Decoction group,and the donepezil hydrochloride group was significantly improved.The activity of5-HT in the serum of the rats in the low-dose Shengmakainao Decoction group,the high-dose group of Shengmakainao Decoction,and the donepezil hydrochloride group was significantly improved.The HE staining results of histopathological sections of the rat hippocampus showed that the cells in the hippocampus of the model group were disordered,a large number of nerve cells were necrotic,the glial cells were increased,and some neurons in the cortex were pyknotic and hyperchromatic.The high-dose Shengmakainao Decoction group and the donepezil hydrochloride group were significantly improved and tended to be normal.The serum levels of TNF-a,IL-6 and IL-1β in the model group were significantly improved,and the levels of TNF-a,IL-6,and IL-1β in the serum of the rats in the model group were significantly improved,and the low-dose Shengmakainao Decoction group,Cimicifuga The contents of the above-mentioned inflammatory factors in the high-dose Shengmakainao Decoction and the donepezil hydrochloride group were significantly inhibited;the results of Western blot assay showed that the protein expressions of TLR4 and NF-κB p65 in the brain tissue of the rats in the model group were significantly increased.Shengmakainao Decoction can inhibit the overexpression of TLR4 and NF-κB p65 in the brain tissue of VD rats.The results of TUNEL assay showed that the positive cell rate in the hippocampus of rats in the model group increased significantly,and high-dose Shengmakainao Decoction could significantly inhibit the apoptosis in the hippocampus of VD rats.Western blot results showed that the protein expressions of Bax and Cleaved-caspase3 in the brain tissue of the model group were significantly increased,the protein expression of Bcl-2 was extremely significantly decreased,and Shengmakainao Decoction was down-regulated.Rat brain tissue Bax and Cleaved-caspase3 protein expression,up-regulated Bcl-2 protein expression.Conclusion: Shengmakainao Decoction can improve the learning and memory ability of VD rats,inhibit the activity of AchE in the serum of VD rats,increase the activity of 5-HT in the serum of VD rats,and improve the pathological changes in the hippocampus of the rats.It has the effect of improving brain injury.Shengmakainao Decoction can inhibit the excessive secretion of inflammatory factors TNF-α,IL-6and IL-1β in the serum of VD rats by regulating the TLR4/NF-κB signal transduction pathway,exerting its anti-inflammatory effect.Shengmakainao Decoction can exert its anti-apoptotic effect by regulating the expression levels of apoptosis-related proteins Bax,Bcl-2 and Cleaved caspase-3 in the brain tissue of VD rats.