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The Effects And Mechanisms Of Peritubular Capillary On Renal Interstitium Fibrosis

Posted on:2011-01-28Degree:MasterType:Thesis
Country:ChinaCandidate:Y ChenFull Text:PDF
GTID:2154360305484603Subject:Academy of Pediatrics
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[Objection] The dissertation investigates the correlation between peritubular capillary and renal interstitium fibrosis in unilateral ureteral obstructions mice in order to study the effects and mechanisms of progression renal disease..[Methodology] 64 healthy male KM mice were randomly divided into 2 groups:①unilateral ureteral obstructions group(UUO, N=32): was operated by ligation of right urter;②Sham operated group (Sham, N=32) was operated by sham surgery. 8 mice of different groups were killed on the 7th, 14th, 21st and 28th day. The blood and renal tissue aliquot were collected .At each time point itams were detected as follows:①ratio of right kidney weight/body weight, serum urea nitrogen (BUN) and serum creatinine(SCr).②The percentages of CD133+/VEGFR2+cells in peripheral blood mononuclear cells was evaluated by flow cytomerty.③Morphological changes of renal tissue were observed by HE and Masson stain and were investigated through light microscope. The method of renal interstitial fibrosis evaluation was used to evaluate the degree of renal fibrosis.④Immuno-histochemistry method was performed to investigate the number of expression cell of CD34+in order to evaluate the peritubular capillary(PTC),as well as NF-κB,VEGF and eNOS.[Results]①Ratio of right kidney weight/body weight: The ratio of right kidney weight/body weight in UUO group increased in time-dependent manner and was obviously higher than Sham group at every time point(P<0.05).②BUN and Scr: The level of BUN and Scr in each group increased 1 week later without significant differences(P>0.05). The level of BUN in UUO group were much higher than Sham group(P<0.05)2 weeks after the operation while they were no remarkable difference in the latter time(P>0.05). The level of Scr in UUO group reached to the climax a weeks later and then decreased after 3~4weeks, which was much higher than Sham group(P<0.05).③The percentages of CD133+/VEGFR2+cells in peripheral blood mononuclear cells in UUO group and Sham group reached to the climax 1 week after the operation. There was a reducing trend of each group as time proceeded. Percentages of CD133+/VEGFR2+cells in UUO group was obviously lower than those in Sham group 3~4weeks (P<0.05).④Renal interstitial fibrosis evaluation:The degree of renal interstitial fibrosis evaluation in UUO group increased in time-dependent manner.⑤PTC:The number of PTC in UUO gradually decreased after the surgery. Compared to Sham group, the level of PTC was lower in UUO group at 2~4weeks(P<0.05).⑥The expression of VEGF in UUO group was light up-regulated after the operation without significant differences(P>0.05)The expression of VEGF in UUO group began decrease at 2 weeks later .There was a significant difference between UUO group and Sham group 2 weeks later(P<0.05).⑦The expression of eNOS in UUO group began decrease after surgery .There was significant difference between UUO group and Sham group at 2 week later(P<0.05).⑧The expression of NF-κB in UUO group gradually increased and reached to the climax after 4 weeks, which had remarkable higher than Sham group(P<0.05).There was negative linear correlated with renal interstitial fibrosis degree and the number of PTC .The direct linear correlation was found between the number of PTC and VEGF in UUO group , as well as eNOS . There were no significant linear correlation between percentages of CD133+/VEGFR2+cells and the number of PTC. [Conclusion]①The number of PTC brought down markedly in renal interstitial fibrosis. There was negative linear correlated with renal interstitial fibrosis degree and the number of PTC .②The down-regulated of VEGF and eNOS , the up-regulated of NF-κB could have effects on decreased of PTC.③The increasing number of CD133+/VEGFR2+ cells at early stage of UUO had inconspicuous effect on PTC, which could be induced by disorder function and inadequate number of CEPCs, as well as unsuitable environment of regeneration.
Keywords/Search Tags:mice, renal interstitium fibrosis, circulating endothelial progenitor cells, peritubular capillary
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