益肺宣肺降浊方调节STAT5/RIPK3/MLKL通路干预VaD坏死性凋亡的实验研究OA

Objective:To investigate the effect and mechanism of Yifei Xuanfei Jiangzhuo Formula on necrotic apoptosis in vascular dementia(VaD)model rats,this study takes the STAT5/RIPK3/MLKL pathway as the starting point.Methods:In this study,50 male SD rats were selected,of which 40 were established using the bilateral common carotid artery permanent ligation(2-VO)method.They were randomly divided into a model group,a low-dose group of YifeiXuanfeiJiangzhuo Formula,a high-dose group,and a donepezil hydrochloride group.Additionally,10 SHAM group rats were also included.Using Morris water maze test to evaluate the learning and memory behavior of rats;H&E staining and Nissl staining were used to analyze the patholog-ical morphology of rat hippocampal tissue;Immunofluorescence staining was used to observe the positive expression of STAT5 and p-RIPK3 in the hippocampal tissues of rats in each group;ELISA method was used to detect the levels of IL-10 and TNF-α factors in the serum of rats in each group;Real time PCR was used to detect the mRNA levels of S T A T 5,F A D D,iNOS,and HO-1;Western blot was used to detect the expression of STAT5,p-RIPK3/RIPK3,p-MLKL/MLKL,and FADD proteins in hippocampal tissue.Results:Compared to the SHAM group,the hippocampal tissue of the model group rats showed significant pathological changes,with significantly prolonged escape latency(P<0.05)and significantly reduced platform crossing times(P<0.05),indicating impaired spatial learning and memory function.The level of TNF-α in rat serum increased while the level of IL-10 decreased;The positive expression levels of STAT5 and p-RIPK3 increased in hippocampal tissue;The mRNA expression of S T A T 5,F A D D,iNOS,and HO-1 increased in hippocampal tissue.The protein expression levels of STAT5,p-RIPK3/RIPK3,p-MLKL/MLKL,and FADD also increased in hippocampal tissue.Compared to the model group,the YifeiXuanfeiJi-angzhuo Formula significantly reduced hippocampal tissue damage and improved learning and memory abilities in VaD rats.It regu-lated the levels of IL-10 and TNF-α factors in serum,reduced the mRNA levels of STAT5,FADD,iNOS,and HO-1,as well as the positive expression levels of STAT5 and p-RIPK3 in hippocampal tissue,and inhibited the protein expression of STAT5,p-RIPK3/RIPK3,p-MLKL/MLKL,and FADD(P<0.05).Conclusion:YifeiXuanfeiJiangzhuo Formula alleviates the pathologi-cal manifestations and inflammatory response of VaD rats by inhibiting the necrotic apoptosis pathway,thereby improving their memory and learning abilities.