Intervention Of Banxia Baizhu Tianma Decoction(BBT) On Vascular Endothelial And Brain Injury Induced By Sleep Deprivation

Objective:To investigate the effect and molecular mechanism of BBT in improving vascular endothelial dysfunction and brain tissue injury induced by sleep deprivation.Methods:In this study,we established a sleep deprivation model to explore the intervention effect of BBT on endothelial and brain tissue injury caused by sleep deprivation.Network pharmacology screening,construction of sleep disorders 、endothelial injury and BBT shared target network,and signal pathway enrichment analysis based on KEGG and GO database.32 rats were randomly divided into four groups: control group、SD group、SD+BBTL and SD+BBTH,eight rats in each group.Blood pressure was measured by tail artery.Open field test was used to observe the behavior of rats.HE staining was used to observe the pathological changes of thoracic aorta and brain.Vascular ring test was used to detect the contraction function in thoracic aorta caused by PE and 5-HT;endothelium-dependent relaxation in thoracic aorta and mesenteric artery caused by ACh and endothelium-independent relaxation in thoracic aorta caused by SNP.ELISA was used to detect the contents of 5-HT、5-HIAA、ACh and ACh E in thoracic aorta、hypothalamus and hippocampus and ET-1 and c GMP in thoracic aorta.The related indexes of oxidative stress(MDA、CAT、SOD、GSH-Px and T-AOC)in serum and thoracic aorta were detected by spectrophotometry.Griess method was used to determine the content of NO in thoracic aorta.The expressions of PI3K、AKT、e NOS、p-AKT and p-e NOS were detected by Western blot.Results:1.Network pharmacology showed:BBT、sleep disorder and vascular injury have 16 shared targets.Go analysis showed that they were closely related to NO biosynthesis,KEGG analysis was closely related to PI3K/Akt and e NOS/NO/c GMP pathway.2.Blood pressure showed:Compared with the control group,the systolic blood pressure increased in the sleep deprivation group(P < 0.01)and the diastolic blood pressure also increased(P < 0.05).Compared with SD group,diastolic blood pressure in SD+BBTL was lower(P < 0.05);systolic blood pressure and diastolic blood pressure in SD+BBTH group were lower(P < 0.01).3.Open field experiment showed that: Compared with the control group,the horizontal and vertical scores of SD group increased on the third day(P < 0.01).Compared with SD group,the horizontal and vertical scores of SD+BBTL group decreased on the fifth day(P < 0.05),and the horizontal score of SD+BBTH group decreased on the third day(P < 0.01)and the vertical score decreased on the fifth day(P < 0.05).4.The results of HE staining showed that compared with the control group,the thoracic aorta endothelium in the SD group was significantly damaged,and cells in brain were scattered and swollen,and amount of inflammatory cells were infiltrated.Compared with SD group,SD+BBTH group could improve the exfoliation of aortic endothelial cells and brain injury.5.Mesenteric endothelium dependent relaxation showed: Compared with control group,there was no significant difference in ACh induced mesenteric artery relaxation in SD group(P > 0.05).6.The results of thoracic aorta contraction were as follows:Compared with the control group,the contraction of thoracic aorta induced by PE or 5-HT in SD group significantly increased(P < 0.01).Compared with SD group,the contraction of thoracic aorta induced by PE or 5-HT in SD+BBTH group significantly decreased(P < 0.01).7.Endothelium dependent relaxation of thoracic aorta:Compared with control group,ACh induced relaxation of thoracic aorta in SD group significantly decreased(P < 0.01).Compared with SD group,ACh induced relaxation of thoracic aorta in SD+BBTL group or SD+BBTH group increased(P < 0.01).8.Endothelium independent relaxation of thoracic aorta:Compared with control group,the relaxation of thoracic aorta caused by SNP in SD group had no significant difference(P > 0.05).9.The changes of 5-HT and ACh in thoracic aorta、hypothalamus and hippocampus showed :Compared with control group,5-HT 、 5-HIAA and ACh in thoracic aorta 、 hypothalamus and hippocampus of SD group significantly decreased(P < 0.01),and ACh E activity significantly increased(P < 0.01).Compared with SD group,5-HIAA in thoracic aorta and 5-HT and 5-HIAA in hippocampus significantly increased in SD+BBTL group(P < 0.01);5-HT、5-HIAA and ACh in thoracic aorta、hypothalamus and hippocampus significantly increased in SD+BBTH group(P < 0.01),and ACh E activity significantly decreased(P < 0.01).10.ET-1、NO and c GMP in thoracic aorta showed:Compared with control group,ET-1 in thoracic aorta of SD group significantly increased(P < 0.01);NO and c GMP significantly decreased(P < 0.01).Compared with SD group,ET-1 in thoracic aorta of SD+BBTL or SD+BBTL group significantly lower(P < 0.01)and NO and c GMP significantly increased(P < 0.01).11.Related indexes of oxidative stress in serum and thoracic aorta: Compared with control group,MDA in serum and thoracic aorta of SD group significantly increased(P < 0.01),CAT、GSH-Px and TAOC significantly decreased(P < 0.01),SOD in serum significantly decreased(P < 0.05)and SOD in thoracic aorta significantly decreased(P < 0.01).Compared with SD group,CAT and T-AOC in serum and thoracic aorta of SD+BBTL group significantly increased(P < 0.01),SOD in serum and thoracic aorta significantly increased(P < 0.05);In SD+BBTH group,MDA in serum significantly decreased(P < 0.01),MDA in thoracic aorta significantly decreased(P < 0.05),CAT in serum and CAT、SOD、GSHPx and T-AOC activities in thoracic aorta significantly increased(P < 0.01);SOD、GSH-Px and T-AOC in serum significantly increased(P < 0.05).12.Western blot results showed:Compared with control group,PI3 K and the phosphorylation levels of AKT and e NOS in thoracic aorta of SD group significantly decreased(P < 0.01).Compared with SD group,PI3 K and the phosphorylation levels of e NOS in thoracic aorta of SD+BBTL significantly increased(P < 0.01),and the phosphorylation level of AKT significantly increased(P < 0.05);PI3K and the phosphorylation levels of AKT and e NOS in thoracic aorta of SD+BBTH group significantly increased(P < 0.01).Conclusions:1.Acute sleep deprivation can cause damage of vascular endothelial function and brain tissue.2.PI3K/AKT/e NOS/NO/c GMP pathway is one of the molecular mechanisms of vascular endothelial damage caused by sleep deprivation.3.BBT can improve vascular endothelial function and brain tissue damage caused by sleep deprivation.