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Mechanism Of Schisandrin In Repairing Of The Diabetes-induced Erectile Dysfunction Of SD Rats Via The RhoA/ROCK Signaling Pathway

Posted on:2019-12-10Degree:MasterType:Thesis
Country:ChinaCandidate:P P GuoFull Text:PDF
GTID:2394330566479311Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: Sprague Dawley(SD)rat model of diabetes-induced erectile dysfunction(DIED)was prepared,treated with different concentrations of schisandrin,to compare the RhoA,p-MYPT-1,eNOS,NO,MDA and SOD changes before and after treatment and explore the possible mechanism of schisandrin repairing of on erectile function in rats.Method:1.Screening DIED rats: male SD rats were injected with streptozotocin(STZ)to prepare diabetes mellitus(DM)rats.After 8 weeks,apomorphine(APO)was injected to screen Diabetes-induced erectile dysfunction(DIED)rats.2.Grouping and treatment: the rats were randomly divided into the normal control group(NC group),diabetes-induced erectile dysfunction group(DIED group),low-dose schisandrin group(5mg/kg/d,L-S group),middle-dose schisandrin group(10mg/kg/d,M-S group),high-dose schisandrin group(20mg/kg/d,H-S group).3.After 8 weeks of gavage(once a day),APO was given again to observe the erection of the penis in rats.rats were stimulated by electrical stimulation of the penis cavernous nerves in the penis,and the ICP,MAP were measured.4.During the experiment,the blood glucose was measured once a week,and the body mass was measured once four weeks.After the experiment,the inferior vena cava blood of rats were collected to measure the level of ALT,AST,ALP,SR,Na,K and Ca.5.Pulldown assay was used to determine the activity of GTP-RhoA,and Western blot to detect the phosphorylated myoglobin phosphatase targetsubunit 1(p-MYPT-1)in penile tissue.Determination of NO concentration by nitrate reductase method.Nitric oxide synthase activity assay kit was used to determine the concentration of eNOS in penile tissue.TBA method was used to determine MDA concentration,and hydroxylamine method to determine SOD concentration.Results:1.Before the injection of STZ,there was no statistical difference between the body weight and blood glucose(P>0.05).After 3 days of STZ injection,the body weight of rats in group DM was significantly lower than that in NC group,and the blood sugar increased significantly(P<0.002).After 4 weeks and 8 weeks of STZ injection,the body weight of DM rats was significantly lower than the NC group,and the blood sugar increased significantly(P<0.002).Compared with the NC group,the body weight of the rats in the low,middle and high dose groups decreased significantly before the gavage,and the blood glucose increased significantly(P<0.001).In addition to the NC group,there was no significant difference in body weight and blood glucose by multiple comparison(P>0.05).After 4 weeks and 8 weeks of gavage,compared with the NC group,the body weight of the low,middle and high dose group and DIED group decreased significantly,and the blood glucose increased significantly(P<0.001).In addition to the NC group,there was no significant difference in body weight and blood sugar by multiple comparison(P>0.05).2.After 8 weeks of gavage,the erectile rate in group NC was 100%,the erectile rate in DIED group and L-S group was 0.0%,the erectile rate in group M-S was 16.6%,and the erectile rate in H-S group was 28.5%.3.Before electrical stimulation,there were no significant differences between the groups of the baseline ICP,MAP and ICP/MAP(P>0.05);The MAP value among all groups had no significant difference when the electrical stimulation group(P>0.05).When the electrical stimulation group,compared with the NC group,low,middle and high dose group and DIED group,the ICP and ICP/MAP of rats decreased(P<0.001);compared with group DIED,ICPin low,middle and high dose group increased significantly(P<0.05),compared with DIED group,ICP/MAP increased significantly in middle and high dose group(P<0.05).4.There was no significant difference in serum ALT,AST,ALP,SR,Na,K and Ca levels in the serum of rats.(P>0.05).5.The expression of eNOS and NO decreased significantly in the DIED group,compared with the NC group,the difference was statistically significant(P<0.002);compared with DIED group,low,middle and high dose group of eNOS,NO expression gradually increased,the difference was statistically significant(P<0.05).In the low,middle and high dose group,the difference multiple comparison was statistically significant L-S group compared with H-S group(P<0.002).6.Compared with NC group,the DIED group MDA expression increased significantly,the DIED group SOD expression was significantly decreased,the difference was statistically significant(P<0.05).Compared with DIED group,MDA and SOD expression in low,meddle and high dose group decreased gradually,the difference was statistically significant(P<0.05).In the low,middle and high dose group,there was a significant difference between the multiple comparison L-S group and H-S group(P<0.05),and the expression level of MDA in H-S group was lower,and the expression level of SOD in the H-S group was higher.7.In the DIED group,the expression of GTP-RhoA and p-MYPT-1increased significantly,compared with the NC group the difference was statistically significant(P<0.05);compared with DIED group,low,middle and high dose group,GTP-RhoA and p-MYPT-1 expression decreased gradually,there are statistically significant difference(P<0.05).In the low,middle and high dose group,the GTP-RhoA expression of multiple comparison L-S group was significantly different from that of H-S group(P<0.05).In the low,meddle and high dose group,there was no significant difference in the expression of p-MYPT-1 in the multiple comparison group between the L-S group and the H-S group(P>0.05).Conclusion:1.The damage of oxidative stress exists in the penis tissue of SD rats with diabetic erectile dysfunction.2.Schisandrin could improve erectile function in SD rats with diabetic erectile dysfunction,especially in high dose group(20mg/kg/d).3.The possible mechanism of Schisandrin to improve erectile dysfunction in diabetic SD rats: to increase the expression of eNOS and NO by inhibiting the expression of RhoA/Rho kinase.4.The concentration of schisandrin in a certain range has no significant effect on the liver and kidney function and electrolyte in diabetic SD rats.
Keywords/Search Tags:Erectile dysfunction, Schisandrin, Diabetic rats, Oxidative stress, RhoA, p-MYPT-1
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