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Protective Effect And Its Mechanisms Of Estrogen On Intestinal Ischemia Reperfusion Injury In Pubertal Rats

Posted on:2005-04-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:D H LiuFull Text:PDF
GTID:1104360125467406Subject:Academy of Pediatrics
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Purpose: To investigate the role of estrogen in intestinal ischemia reperfusion (I/R) injury, the intestinal I/R model of pubertal rats was established to observe the possible effect of estrogen on I/R injury under different serum concentration of 17(-estradiol created by ovariectomy or 17(-estradiol administration,and to study its mechanisms.Material and methods:60 pubertal female rats were divided into 4 groups by randomized: ovariectomy group(OVX group), control group(CON group),variectomy+100ug/kg dose of 17(-estradiol group(OVX+E2 group) and variectomy +500ug/kg dose of 17(-estradiol group(OVX+5E2 group). Rats were ovariectomized and injected subcutaneously with olive oil (OVX group) or 17(-estradiol (100 or 500ug/kg/every other day, OVX+E2 or OVX+5E2 group) for 4 weeks. Other rats underwent sham ovariectomy as control group. The rats in each group (n=15) were subjected to SMA occlusion and then followed by 1h(n=5), 6h (n=5), or 24h(n=5) reperfusion. Determination the Serum concentration of 17(-estradiol by radioimmunoassay and histopathologic score of intestine specimens, Determination the content of NO and MDA and the activity of MPO by chemical measurement and the content of TNF-α by ELISA in Serum samples. Determination the activity of iNOS and MPO by enzyme measurement,and the expression of iNOS,TNF-α and ICAM-1 mRNA by real time PCR。Results: The serum concentration of 17(-estradiol was increased from OVX group to OVX+5E2 group in turn, the serum concentration of 17(-estradiol between groups was different(P<0.01). In OVX, CON, OVX+E2, and OVX+5E2 group, histopathologic score was 3.31±0.12, 3.00±0.09, 2.57±0.12, and 2.98±0.08, respectively. The expression of iNOS mRNA was 3.85±0.42, 4.86±0.76, 5.17±0.34, and 4.25±0.41 log copies, respectively. Lower histopathologic score but higher iNOS mRNA expression in tissue were fund in OVX+E2 group than in any other group (P<0 .01). The level of iNOS activity paralleled the expression of iNOS mRNA. Compared with other groups, the serum content of NO in OVX+E2 group was highest(P<0.05). Lower expression of TNF-α mRNA and ICAM-1 mRNA in tissue also was fund in OVX+E2 group than in any other group (P<0.01). the serum content of TNF-α in OVX+E2 group was lower, only higher than that in CON group, the serum content of TNF-α between groups was different(P<0.05 or P<0.01). Compared with OVX and OVX+5E2 group, Lower activity of MPO in tissue was fund in OVX+E2 group(P<0.01).The activity of MPO and content of MDA in serum after I/R injury were lower than that of MPO and MDA before I/R injury in CON, OVX+E2, OVX+5E2 group,but reversely in OVX group. Compared with OVX and CON group, the serum ⊿MPO and ⊿MDA values in OVX+E2 group were lower(P<0.01). Positive linear correlation was found between the serum concentration of 17(-estradiol and iNOS mRNA expression and its activity in tissue; also between histopathologic score and TNF-α mRNA expression in tissue, MPO activity in tissue and serum ⊿MDA values. Negative linear correlation was found between the serum concentration of 17(-estradiol and histopathologic score, serum content of TNF-α, ICAM-1 mRNA expression in tissue, serum ⊿MPO and ⊿MDA values; also between histopathologic score and iNOS mRNA expression and its activity in tissue. There were positive linear correlation between iNOS activity in tissue and serum content of NO,between MPO activity in tissue and serum content of TNF-α and ICAM-1 mRNA expression in tissue, and also between the serum ⊿MPO and ⊿MDA values. There were negative linear correlation between serum content of NO and ICAM-1 mRNA expression in tissue.Conclusion: 1.Protective effect of estrogen on intestinal I/R injury in pubertal rats. 2. The probable mechanisms of protective effect of estrogen on intestinal I/R injury in pubertal rats as follows: ①; by enhancing the effect of NO/NOS system. ②; by inhibiting inflammatory response of TNF-αand ICAM-1. ③; by inhibiting neutrophil infiltration and activation. ④; by reducing the degree of lipid preoxidation. 3.P...
Keywords/Search Tags:Estrogen, Small intestine, Ischemia reperfusion injury, Inducible nitric oxide synthase, Nitric oxide, Tumor necrosis factor-a, Intercellular adhesion molecules-1, Myeloperoxidase, Oxygen-derived free radicals, Malondialdehyde
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