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일측 요관폐쇄에 의한 실험적 수신증에서 신조직내 MCP-1 및 TNF-α유전자 발현
나가량,황평주,김종학,구영선,강민규,서광선,이강욱,신영태 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.2
Early cellular and molecular derangements have been suggested as potential pivotal factors for the development of renal injury, such as interstitial fibrosis after the experimental hydronephrosis. Several recent studies have been demonstrating that one of the initial events taking place in the progressive renal injury process is the mononuclear cell infiltration in the glomeruli and tubulointerstitiuim. In order to evaluate the renal light microscopic findings as well as the renal cortical MCP-1 and TNF-α gene expressions which are modulating inflammatory process and the recruitment of mononuclear cells in many experimental models of renal injury, Sprague-Dawley rats underwent unilateral ureteral obstruction (UUO) and sham operation under the thiopental sodium anesthesia(50 mg/kg intraperitoneal injection). Three and 7 days after surgery, rats were sacrificed. By the competitive RT-PCR, the levels of TNF-α and MCP-1 mRNA in renal cortical tissues were measured. The magnitude of mononuclear cell infiltration and interstitial widening were evaluated by standard point counting method. The level of MCP-1 gene expression was significantly increased in UUO group compared to sham group at 3 and 7 days after surgery(UUO 3 days 8.99 ± 0.45, UUO 7 days 11.2 ± 0.26, sham 3 days 1.00 ± 0.08, sham 7 days 0.94 ± 0.05, p < 0.01, p < 0.01, mean ± SEM, respectively). The level of MCP-1 mRNA at 7 days after surgery was significantly higher than that at 3 days in UUO group. The TNF-α gene expression level of UUO group was also significantly higher than that of sham group at 3 and 7 days after surgery(UUO 3 days 1.73 ± 0.16, UUO 7 days 2.03 ± 0.21, sham 3 days : 1.00 ± 0.06, sham 7 days 1.09 ± 0.03, p < 0.01, p < 0.01, respectively). But there was no significant difference between the levels at 3 and 7 days after surgery in UUO group(p>0.05). On the light microscopic examination, the relative volume of interstitium (RVI) and the total count of infiltrated mononuclear cells(MCC) at 3 and 7 days after surgery in UUO group were also significantly higher than those of sham group(RVI ; UUO 7 days 14.9±1.0%,sham 6.0±0.7%, MCC; UUO 7days 34.0± 1.6, sham 3.7± 0.6, p < 0.01, p < 0.01, respectively). In conclusion, we speculated that the early up-regulation of MCP-1 and TNF-α genes of renal cortical tissue in this experimental hydronephrosis model is closely related to the mononuclear cell infiltration and tubulointerstitial fibrosis.
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