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Objective: This study through the establishment of paraquat (paraquat, PQ) poisoning kidney injury model in rats, the observed changes in nephrotic Science, heme oxygenase the -1 (Heme oxygenase-1, HO-1) and inducible nitric oxide synthase (inducible NOS, iNOS) expression, and melatonin (melatonin, MT) on the above indicators, to further investigate the therapeutic effects of acute PQ poisoning pathophysiological mechanisms of renal injury and the MT. Methods: Healthy adult Spragne-Dawley (SD) rats 182, male and female, were randomly divided into three groups: blank control group (A) 42 (B) 70 exposure groups, the MT the treatment group (C group) 70. B, C group PQ (25mg/kg) intraperitoneal injection and treated with intraperitoneal injection of the A-group with normal saline; exposure 15min within the the C group MT10mg/kg · d A, B group the same amount of saline injected intraperitoneally. Each group at 3h, 6h, 12h, 1d, 2d, 3d, 5d 6 rats ether anesthesia, abdominal aortic blood were measured in serum urea nitrogen (blood urea nitrogen, BUN), creatinine (creatine, Cr ) level; the right kidney hematoxylin - eosin (with hematoxylin-eosin, HE) staining pathological changes, immunohistochemistry to detect the expression of HO-1 and iNOS; left kidney upper pole determination of tissue homogenates SOD, MDA and GSH-Px The activity; frozen for lower pole left kidney, Reverse Transcription-Polymerase Chain Reaction method determination of the HO-1mRNA expression. Results: ① rat poisoning performance: exposure to group B after 30min-2h symptoms of poisoning, including respiratory, mental, nervous, digestive and urinary systems, etc. The most obvious ,1-3d, 3d gradually reduce. Group C than in group B significantly reduced, especially respiratory symptoms. Compared with group A, B group lost weight significantly alleviate the obvious group C. (2) pathological observation: A group organizational structure is clear, no edema, vacuolar degeneration, cloudy swelling and necrosis. Compared with group A, group B organizational structure clarity decreased after exposure 3h tubule cells of the cortex swelling, small narrow tube cavity, interstitial congestion, edema, aggravated with time, 1d peaked to the experimental In the end, no relief. Part of the ball, medullary involvement. There may be severe pyknosis, cell structure disappeared, but its scope does not increase with time. Epithelial nuclear pyknosis and medulla compared with group B, group C, glomerular involvement rare lighter other pathological damage and mitigate the trend. ③ biochemical markers observed: one day after exposure to 5d, the serum BUN B was significantly higher than in group A (P lt; 0.05); while group C than in group A after exposure 3d was significantly higher (P lt; 0.05) but the increase was below the B group, the difference was statistically significant (P lt; 0.05). Groups serum Cr mostly within the normal range, only a small number of higher than normal. The ④ MDA determination: group B was significantly higher exposure 3h, 2d, reached the peak, followed by a slow decline, compared with group A, 6 h after exposure to the 3d the difference was statistically significant (P lt; 0.05) 5d when the difference was no longer statistically significant (P gt; 0.05). Group C compared with group A also increased, but both differences were not statistically significant (P gt; 0.05) at all time points, compared with group B rises slowly and increases to reduce exposure 6h difference was statistically significance (P lt; 0.05), 3d both not statistically significant (P gt; 0.05). ⑤ SOD determination: group B decreased significantly after exposure 3h, after a slow increase, compared with group A, after poisoning 3h to 3d the difference was statistically significant (P lt; 0.05), significantly lower than 5d Group A, but is no longer statistically significant (P gt; 0.05). Increased substantially exposed to group C after 12h, the difference was statistically significant (P lt; 0.05) compared with group A, 2d reached a peak, then maintained at a high level, 5d began a downward trend, but still significantly higher than the A group (P lt; 0.05); each time point B group, the difference had statistical significance (P lt; 0.05). ⑥ GSH-Px determination: group B significantly reduced after exposure 3h, compared with group A, the difference was statistically significant (P lt; 0.05), after rising rapidly, 1d, reached the peak and remain at that level, but with the A group, the difference was not statistically significance (P gt; 0.05). Group C, 3 h after exposure was significantly higher compared with group A, the difference was statistically significant (P lt; 0.05), and reached the peak at 6h after maintained at a high level until the end of the experiment, no downward trend; Group B phase ratio at each time point differences were statistically significant (P lt; 0.05). ⑦ renal tissue iNOS expression: A group of not more than expression; B group after exposure 3h appear in the cytoplasm of the cortex of the renal tubular epithelial cells and glomerular endothelial cells express, 6h after immunohistochemical score (Immunohistochemistry score IHS) was significantly higher compared with group A, the difference was statistically significant (P lt; 0.01), 1d reached a peak and thereafter maintain a strong expression; C group after 3h also express the IHS significantly elevated, 12h after the , compared with group A, the difference was statistically significant (P lt; 0.05) was expressed at low levels in the future, 5d A group difference (P gt; 0.05) 6h after exposure to the end of the trial when the IHS significantly lower in group B (P lt; 0.05). ⑧ renal tissue expression of HO-1: A group of more than not express; group B after exposure 3h in the membrane and cytoplasm of tubular epithelial cells in the cortex expression, IHS pressure difference compared with group A statistical significance (P lt; 0.05), 1d peaked before decreasing, the 5d still positive expression, but compared with group A, IHS difference was no longer statistically significance (P gt; 0.05); C group after 3h also express the IHS was significantly higher than that in group A and group B, the differences were statistically significant (P lt; 0.05), 1d reached a peak, after weakening trend 5d is still a strong expression, compared with group A, IHS significantly increased, and the difference was statistically significant (P lt; 0.05), compared with group B, IHS difference was no longer statistically significant (P gt; 0.05). The ⑨ HO-1mRNA the expression: A group of not more than expression; 3h HO-1mRNA enhanced expression of group B after exposure, compared with group A, the difference was statistically significant (P lt; 0.05), 1d reached a peak relative expression A group of 2.28 times, then gradually decreased after exposure 3d, only a small amount of expression compared with group A, the difference was no longer statistically significance (P gt; 0.05). Group C the 3h HO-1mRNA expression after exposure significantly increased, compared with group A, the difference was statistically significant (P lt; 0.05), 1d reached a peak relative expression level was 3.03 times the group A, followed by a slow decline to 5d still expressed, the difference was statistically significant (P lt; 0.05) compared with group A. Compared with group B, after exposure 6h to 3d group C expression of HO-1mRNA significantly enhanced, the difference was statistically significant (P lt; 0.05), the both no statistical significance (P gt 5d; 0.05) . Conclusion: The present study demonstrated that PQ25mg/kg intraperitoneal injection and treated is made reliable way to do PQ poisoning kidney injury in animal models, worthy of promotion in PQ poisoning; paraquat poisoning rats MDA content, SOD activity decreased l, and after the first drop of GSH-Px activity imbalance between oxidative damage and oxidation - anti-oxidation system is an important mechanism to cause kidney damage. INOS involved in the pathogenesis of renal injury; protective effect of MT PQ poisoning kidney damage, which may by HO-1, iNOS play a role, but the regulatory pathway needs to be further explored.
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