The Clinical Significance Of Hypoxia Inducible Factor-1 Alpha (hif-α) Expression In Portal Hypertensive Gastropathy (phg) With Cirrhosis

Objective1. Detecting the expression and distribution of HIF-1αmRNA and protein molecule in the gastric mucosa of portal hypertensive gastropathy(PHG) patients and healthy people; Investigating the relationship between the expression of HIF-la mRNA and protein molecule in gastric mucosa and the endoscopic classification of portal hypertensive gastropathy; Investigating the relationship between the expression of HIF-1αmRNA and protein molecule and the Child-Pugh classification of cirrhosis patients.2.By studying the expression and distribution of HIF-la mRNA and protein molecule in gastric mucosa, to provide an opportunity for finding a new marker for clinical diagonosis, therapy and prognosis of PHG.MethodsAll of 60 tissue samples were collected from patients with PHG in digestive medical department of Jinan Military General Hospital from August 2009 to December 2009,and were categorized as a study group,all of which including fifty-seven cirrhosis patients and three idiopathic portal hypertension patients without no cirrhosis.And according to the Child-Pugh classification of cirrhosis, there were sixteen Child-Pugh A,twenty-five B and sixteen C patients. According to the classification method of Mc Cormack for PHG,30 cases of PHG patients were severe type,30 cases were mild type. Besides,we selected thirty normal tissue samples from healthy people as external control group in this study.The nomal gastric mosoca(gastric Antrum) from HPG patients were selected as internal control group. Immunohistochemistery techenique was utilized to detected protein molcule, real-time PCR techenique was utilized to detecte mRNA molecule of HIF-la, SPSS16.0 software package was used as the statistical treatment method.When P-values<0.05 were considered to be statistically significant.Results1. The protein of HIF-la was mainly expressed in cytoplasm, and was brown and granular.the protein was not or lowly expressed in normal gastic mucosa.Of the three groups:the healthy people, the mild type PHG and the severe type PHG patients, the positve rate of HIF-1αprotein in the severe type PHG gastic mucosa was higher than that in mild type PHG, and positve rate of HIF-1αproten in mild type PHG is higher than in healthy people. There was significant statistical difference among these three groups(p<0.05), the positive rate of HIF-1αprotein was increased following the severity of PHG, the expression of HIF-la protein was linear correlative with the severity of PHG. (p<0.05)2. The positve rate of HIF-1αprotein in diseased section gastic mucosa(gastic fundus and gastic corpus) was higher than in non-diseased section mucosa (gastic antrum). This happened in both mild type PHG and severe type PHG patients.(p<0.05)3. According to the Child-Pugh classification method of cirrhosis, there was no significant statistical difference in the positve rate of HIF-la protein among the three groups patients of Child-Pugh A, B and C.(p=0.684)4. HIF-la mRNA was amplificated not only in gastric mucosa of healthy people, but also in gastric mucosa of mild type and severe type PHG patients (including diseased section and non-diseased section). Of the three groups:the healthy people, the mild type PHG patients and the severe type PHG patients, there was no significant statistical difference in the relative amplificated copies of HIF-la mRNA. (p>0.05)5. The relative amplificated copies of HIF-1αmRNA in diseaed section gastic mucosa (gastic fundus and gastic corpus) was not higher than in non-diseased section(gastic antrum) mucosa(p>0.05).This result happened in both the mild type PHG patients and the severe type PHG patients.6. According to the child-pugh classification method of cirrhosis, there was no statistical significant difference of the relative amplificated copies of HIF-la mRNA among the three groups patients:Child-Pugh A,B and C.(p>0.05)7. There was no correlationship between the classification of PHG and the child-pugh classification, the severity of PHG was not increased with the severity of the child-pugh classification. (p>0.05)ConclusionsThe expression level of HIF-1αprotein in diseased section gastric mucosa was higher than in non-diseased section gastric mucosa in PHG; The expression level of HIF-la protein of diseased section gastric mucosa in PHG was higher than in healthy people's gastric mucosa. Of the three groups:the healthy people, the mild type PHG patients and the severe type PHG patients, there was no significant statistical difference in the relative amplificated copies of HIF-la mRNA.The expression level of HIF-1αmRNA was regulated by hypoxia, and was irrelative with Child-Pugh classification of cirrhosis, it was not correlative with the endoscopic classification. HIF-la may be used as a new marker for clinical diagonosis, therapy and prognosis of PHG.