| Objective To observe the influence of intermedin(IMD) on renal interstitial fibrosis, we make the model of rats unilateral ureteral obstruction(UUO) and pump IMD to rats with the mini-osmotic pumps.Methods (1) Forty male Wistar rats were randomly divided into two groups:the sham-operation group (n=10) underwent the left ureteral dissection, additional30rats were unilateral ureteral obstruction and divided into the model group (UUO), the Losartan group, the IMD group (each group n=10).①The Losartan group were administered a does of losartan suspension20mg/(kg·d) by gastric gavage after UUO till death.②The IMD group:The rats dorsal skin incise the approximatelcm long incision, implant pumps that dissolve IMD8-47with saline and inject it to mini-osmotic pumps under the sterile conditions. The pumps open towards the rat dorsal anterior, continuously subcutaneous administrate by the doses of100ng/(kg·h), and ensure that the pumps are good in the subcutaneous.③The sham-operation and UUO groups were administered equal volumes of saline by gastric gavage.(2) At the14,21days of the operation, randomly5rats from each group were blooded by abdominal arotic and obstractive kidneys were taken out. The renal histopathological changes were observed by HE and Masson staining. The urea nitrogen(BUN), serum creatinine (Scr), and hydroxyproline(Pro) of the obstructive kideys were measured by colorimetry. TGF-β1and intermedin were immuno-histochemisty staining and semiquantitative analysis.Results (1) Kidney pathological changes:HE and Masson staining observe under light microscope that the glomeruli and tubular structure of the sham operation group rats were normal. The UUO Groups are renal tubular epithelial cell swelling, vacuolar degeneration, tubular atrophy, obliteration or expansion, diffuse mononuclear infiltration of lymphocytes, interstitial widening, fibroblast proliferation, increased collagen fibers, fibrosis, and fibrosisobvious. Compared with the UUO group, tubular damage and interstitial fibrosis of the Losartan and IMD groups were both reduced.(2) Blood BUN and Scr levels:Compared with the sham-operated group, the level of urea nitrogen (BUN) and serum creatinine (Scr) of UUO group were significantly up-regulated(P<0.01). In comparion with the UUO group, the level of BUN and Scr of the Losartan and IMD groups were lower(P<0.05). The Losartan group compared with the IMD group renal function was improved, but the difference was not statistically significant.(3) Hydroxyproline(Pro) content of renal tissue:The results are the similar to the above.(4) The immunohistochemical staining results:①The expression of transforming growth factor β1(TGF-β1) in the sham-operated group were trace. The UUO groups observed a strong positive for TGF-β1expression. In comparion with the UUO group, the level of TGF-β1in the Losartan group were lower(P<0.05).②Compared with the sham group, IMD positive signal of the remaining three groups in renal interstitial increased. The losartan group IMD percentage of positive staining area is less than the UUO group (P<0.01); and UUO group compared to the the IMD renal tissue IMD positive expression was significantly increased (P<0.05); IMD expression of the IMD group significantly increased compared with the losartan group (P<0.05).Conclusion IMD mitigate the renal interstitial fibrosis, improve renal function, and the mechanism may be antagonize on inflammatory mediators-TGF-β1... |
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