| Part one.Multivariate Analysis for Risk Factors of EsophagealVariceal Hemorrhage in the Patients with CirrhosisObjective:To investigate the statistical significance of gender in the patients of esophageal variceal hemorrhage with cirrhosis.Methods:The patients who were diagnosed with esophageal varices bleeding were admitted in PLA General hospital from April 1987 to January 2008.The age and gender of the patients were recorded.The ninety-two cases which were recorded from January 2006 and January 2008 were divided into two groups according to the internalizing conditions.Group A was the patients who had the history of esophageal varices bleeding,but did not bleed during three months prior to admission.Group B was the patients who had not the history of esophageal varices bleeding.And the patients of Group A and B were divided into two groups according to menostasis age(A1<50 years,A2>50 years,B1<50 years and B2>50 years).The cases of esophageal variceal were collected including of age,gender,liver function Child-pugh grade,staging of esophageal variceal,red color sign,accompany with gastric varices or not,inside diameter of portal vein,bilirubin,albumin and platelet count.The major factors which may influence variceal hemorrhage in the patients with liver cirrhosis were analyzed by Logistic regression mode using software of SPSS 13.0 for Windows.Results:The 2008 cases between April 1987 and January 2008 were summaried.The ratio of male-female was 1.11:1 before 15 years,5:1 between 15 years and 50 years, 2.39:1 after 50 years.The ninety-two cases between January 2006 and January 2008 were analyzed using Logistic regression analysis according to internalized condition. Logistic regression with multivariate analysis revealed that the effect of liver function Child-pugh grade and red color sign on esophageal variceal hemorrhage was significantly statistical significance(X2=5.146,P=0.023;X2=9.158,P=0.003). Multivariate analysis revealed that the effect of gender,red color sign and liver function Child-pugh grade on esophageal variceal hemorrhage was significantly statistical to the patients whose age dimin 50(X2=4.163,P=0.041;X2=4.163,P=0.041;X2=6.506,P =0.011).Multivariate analysis revealed that liver function Child-pugh grade and platelet count significantly affected to the patients with variceal hemorrhage whose age exceed 50 years,but have not ststistical significance(X2=3.179,P= 0.075;X2=3.229, P=0.072).Conclusion:First The gender ratio is different to the patients who was diagnosed with esophageal varices bleeding in AP menopause.The ratio of male is super than female before the age of 50 years.The ratio of female is increase,the ratio of male is decrease after the age of 50 years.Second,liver function Child-pugh grade is risk factor which may influence variceal hemorrhage to the cirrhotic patients.Gender and red color sign are the independent risk factors to variceal hemorrhage before menopause.Part two.The Affect of Estrogen on the Portal Pressure,Esophageal Veins Form and Phenotype Proteinum of VSMC in the Rat Model of Portal HypertensionObjective:To establish a rat model of esophageal varices with portal hypertension through the method of the two-stage ligation of portal vein plus ligation of the left adrenal vein performed.To explore the affect of estrogen on the portal vein pressure,esophageal veins form and phenotype proteinum of VSMC in the process of esophageal varices with portal hypertension. Methods:Eighty femina SD rats were divided into four groups randomly.There were 20 rats in each group.A group was the control group(sham operation)in which portal vein,left adrenal vein and ovarities were divided but not being ligated.The two-stage ligation of portal vein plus liagation of left adrenal vein was performed in Group B.The two-stage ligation of portal vein plus liagation of left adrenal vein accompany with ovariotomy was performed in Group C.The two-stage ligation of portal vein plus liagation of left adrenal vein accompany with ovariotomy and estrogen replacement therapy was performed in Group D.All the rats were normal feeded.The portal vein pressure was detected in 1st,3rd,7th,15thand 30thdays after the operation of portal vein completely ligated.And then the rats were perfused and fixed with 4%paraform after being executed.The sample of esophageal was obtained.The blood vessel form was observed by HE dyeing.The dynamic expression ofα-SMA and Desmin in VSMC of esophageal varices in experient rats were detected.Image-Pro-Plus 6.0 Software was used to detect the optical density.Software of SPSS 13.0 for Windows was used to statistical analysis.Results:The pathology change of esophageal varices could be found in all the experiment groups after the operation of portal vein completely lagated.Portal vein pressure of rats in experiment groups was higher than control group in 1st,3rd,7th,15th and 30thdays after the operation of portal vein completely ligated.There was statistical significance about portal vein pressure comparing esperiment groups with control group.There was no statistical significance about portal venous pressure among the experiment groups in 1st,3rd,7t,15thand 30thdays after the operation of portal vein completely ligated.There was no statistical significance about the blood vessel numbers,summary section area and average section area comparing experiment groups with control group in 1stday after the operation.There was no statistical significance about the blood vessel numbers,summary section area and average section area among the experiment groups comparison in 1stday after the operation.There was statistical significance in the blood vessel numbers,summary section area and average section area comparing experiment groups with control group in 3rd,7th,15thand 30th days after the operation.There was statistical significance in the blood vessel numbers comparing group B with group C in 3rddays after the operation.There was statistical significance in the summary section area and average section area comparing group B with group C in 7th,15thand 30thdays after the operation.There was no statistical significance among the correlated indexes in other different time.There was no statistical significance about the express status ofα-SMA and Desmin existing in the submucosa vein of the lower esophagus in 1stday after the operation comparing experiment groups with control group and among the experiment groups.There was no statistical significance about the express status ofα-SMA and Desmin existing in the submucosa vein of the lower esophagus among the experiment groups in 15thdays after the operation.There was statistical significance express status ofα-SMA and Desmin comparing the experiment groups with control group in 30thdays after the operation. There was statistical significance express status ofα-SMA and Desmin between group B and group C,group C and group D in 30thdays after the operation.There was no statistical significance about the express status ofα-SMA and Desmin in 30thdays after the operation between group B and group D.Conclusion:First A rat model of esophageal varices with portal hypertension can be established with two-stage ligation of portal vein plus liagation of the left adrenal vein. Second there is the change in the phaenotype of VSMC which may be correlated with construction rebuilding of varices during the process of esophageal varices with portal hypertension.Third the relation between the change ofα-SMA and Desmin of VSMC and the lever of estrogen may be exist.Fouth estrogen can promote the blood vessel mature and stable construction after the formation of esophageal varices which may be correlate the prevention of esophageal varices bleeding.Part three:The Effect of Estrognen and Tamoxifen on the Expression of VSMC Phynotype Protein on Rat VSMC invitro Objective:To investigate the affection of 17β-estrodiol and Tamoxifen on the expression of ERαand phynotype protein of femina rat VSMC invitro.Methods:The femina rat VSMC was cultured invitro.VSMC was disposed with 10-9M, 10-8M and 10-7M 17β-estrodiol;10-8M,10-7M and 10-6M TAM;10-6M TAM and 10-7M 17β-estrodiol for 24h.The total mRNA was extracted for further experiment.The ERαandα-SMA relative mRNA fragment concentration was analysis by RT-PCR.Results:17β-estrodiol could elevated the expression of ERs in the group of E2(1),E2(2) and E2(3)(F=25.139,P<0.001).TAM did not affect the expression of ERα,but 10-6M TAM could interrupt the effect of 10-7M 17β-estrodiol.17β-estrodiol could elevated the expression ofα-SMA in the group of E2(1),E2(2)and E2(3)(F=67.017,P<0.001). TAM did not affect the expression ofα-SMA,but 10-6M TAM could interrupt the effect of 10-7M 17β-estrodiol.Conclusion:First Estrongen can elevated the expression of convert VSMC from synthesis type to construction type.Second the changes of VSMC phynotype are depended on estrogen,which can be interrupted by TAM.Third estrogen may be regulate the change of phenotype of VSMC through the ERα. |