Actue Kidney Injury And Expression Of TNF-α In Kidney Of Mice Induced By Agkistrodon Halys Pallas Venom

ObjectiveTo establish a model of actue renal injury in mice and to observe the changes of pathology and expression of TNF-αin kidney induced by Agkistrodon halys Pallas venom.MethodsThree groups were designed in this experiment:group N (0.00 mg/kg ), group L (0.50 mg/kg) and group H (1.00 mg/kg) according to the dose of Agkistrodon halys Pallas venom.All were further divided into four sub-groups at 3 h, 6 h, 24 h and 48 h. A total of 96 Kunming mice were randomly and equally assigned to each sub-group.Each mouse was injected intramuscularly. Renal function was detected.Kidney tissues were harvested for assessing the histopathological changes and histological changes of kidneys were evaluated by the corresponding score system.TNF-αwas detected in kidney by immunohistochemical techniques.Statistical analysis ware is SPSS 13.0.Measurement data were compared with analysis of variance and linear correlation was also used. A difference of P < 0.05 was accepted as significant.Results1 The level of BUN and SCr: Significant difference were observed among group N(0.00 mg/kg), L (0.50 mg/kg) and H (1.00 mg/kg) (P<0.05).Renal function elevated at 24 h and decreased by 48 h in group B (P<0.05), while continues to rise in group H.There was no change in group N(P>0.05).2 Expansion of Bowman's space, degeneration of tubular cells and peritubular capillary congestion were observed both in group L(0.25 mg/kg) and (1.00 mg/kg).3 Pathology score of kidney tissue: Significant difference were still observed among group N(normal control group), L (low-dose group,0.25 mg/kg) and H (high-dose group,1.00 mg/kg) (P<0.05). The score elevated at 6 h and decreased by 48 h in group L (P<0.05),while continues to rise in group H at 3 h (P<0.05).There was no change in group N(P>0.05).4 TNF-αIHS in kidney: Significant difference were still observed among group N(0.00 mg/kg), L (0.25 mg/kg) and H (1.00 mg/kg) (P<0.05). The score elevated at 6 h and decreased by 48 h in group L(P<0.05),while continues to rise in group H at 3 h (P<0.05).There was no change in group N(P>0.05).5 Correlation: The level of BUN was positively correlated with the pathology score of kidney tissue(L;r=0.793,P<0.01;H:r=0.870,P<0.01).So did the level of SCr and the pathology score of kidney tissue(L:r=0.883,P<0.01,H:r=0.891,P<0.01).There were also significant positive correlation between the pathology score and the TNF-αIHS in kidney(L:r=0.835,P<0.01;H:r=0.953,P<0.01).Conclusions1 A model of actue renal injury in mice induced by Agkistrodon halys Pallas venom can be established successfully by intramuscular injection at a dose of 0.50 mg/kg or 1.00 mg/kg .2 The severity of actue kidney injury is related to the dose of venom and there is a certain relationship between the severity and the time.3 The significant positive correlation between the pathology score and TNF-αIHS in kidney suggested that the expression of TNF-αmay be one of the important cytokines in actue injuried kidney induced by Agkistrodon halys Pallas venom.