The Role Of CRH In The Gastrolintestinal Barrier Dysfunction In The Model Of Cerebral Infarction

Objective:To investigate the role of CRH in the gastrolintestinal barrier changes in cerebral infarction and explore it's possible underneath mechanism.Methods:60 male Wistar rats were randomly divided into 6 groups with 10 each:Blank group(group B),sham operation group(group C),infarction group(group I),infarction+α-h-CRH(9-41) ic group(group Aic),infarction+α-h-CRH(9-41) ip group(group Aip),infarction+CRH ip group(group H).Blood samples were taken 24h after operation.The plasma activity of diamine oxidase(DAO) concentration of plasma D-lactate and plasma Lipopolysaccharide(LPS) were measured.24h urine were collected to detect urinary cortisol, urinary catecholamines(norepinephrine and epinephrine) and sucrose excretion.Gastric gross ulcer score and histological score of the gastrolintestinal were also determined. Immunohistochemistry was used to analysis the changes of CRH protein localizing in the gastrointestinal tract.WesternBlot and Realtime-PCR technology were used to detect the CRH protein and CRHmRNA in the hypothalamus and gastrointestinal tract.Results:Cerebral infarction was confirmed by NSS in all groups of rat in group I,group Aic, group H and group Aip.The results of the tendency of 24h urinary cortisol,urinary norepinephrine,urinary epinephrine were concurrent:group I≈group H≈group Aip＞group Aicgroup C≈group B。The results of the tendency of sucrose excretion,gastric gross ulcer score,gastric histological score and hypothalamus CRH protein/mRNA were concurrent: group I≈group Aip＞group Aicgroup H≥group C≈group B.The results of the tendency of plasma activity of DAO,plasma D-lactate,plasma LPS,the gut histological score and gut CRH protein/mRNA content were concurrent:group I＞group Aip≥group Aic≈group H≥group C≈group B.There were positive correlations between sucrose excretion,gastric gross ulcer score,24h urinary cortisol,urinary norepinephrine,urinary epinephrine and hypothalamus CRH protein;between the level of plasma D-lac,plasma activity of DAO, plasma LPS and gut CRH protein.Conclusions:(l)The gastrointestinal tract barrier dysfunction will show up with the activation of HPA axis,SNS and the elvation of CRH protein in the hypothalamus and gastrointestinal tract after cerebral infarction.(2) The infarction related gastrointestinal barrier dysfunction is occure probably not because of cortisol or catecholamine.(3)CRH is closely related to the infarction related gastrointestinal barrier dysfunction.We may suppress this kind of stress related gastrointestinal barrier dysfunction through interfere the activity of CRH in the hypothalamus or the gastrointestinal tissue.(4) Central use of CRH antagonistα-h-CRH(9-41) will suppress the infarction related gastrointestinal barrier dysfunction to a certain degree.(5)Peripheral use of CRH antagonist a-h-CRH(9-41) will suppress the infarction related intestinal but not gastric barrier dysfunction to a certain degree(6) Peripheral use of CRH can suppress the concentration of CRH protein/CRHmRNA in the gastrointestinal tract and hypothalamus.(7)Infarction related gastric barrier dysfunction is correlated with CRH protein in the hypothalamus and stomach,Infarction related intestinal barrier dysfunction is correlated with CRH protein in the intestinal tract but not in the hypothalamus.