Anti-inflammatory Effect Of Atorvastatin On Adriamycin-induced Progressive Nephropathy In Rats

Objective: To investigate anti-inflammatory effect of different dose of atorvastatin on adriamycin-induced progressive nephropathy in rats and to investigate synergistic anti- inflammatory effect of atorvastatin conbined with prednisone or not.Methods:Adriamycin-induced progressive nephropathy was established by unilateral nephrectomy and injecting adriamycin(4mg/kg).Rats were randomly divided into six groups(two control groups and four treatment groups): normal control group (equal capacity distilled water),model control group(equal capacity distilled water),prednisone group(10mg/kg/d), low- dose atorvastatin group(5mg/kg/d),high-dose atorvastatin group(10mg/kg/d),prednisone conbined with high-dose atorvastatin group . Treatment was performed by intragastric administration for 6 weeks. 24-hour urinary protein , serum albumin, blood-lipid ,serum urea nitrogen ,and serum creatinine were checked before and after treatment, and renal pathology was detected after rats were treated for 6 weeks . Immunohistochemistry was used to observe the expressions of NF-κBp65 and MCP-1 in renal tissues, and RT-PCR was used to observe the expressions of NF-κBp65mRNA and MCP-1mRNA in renal tissues.Results:①Between each two group among the six gloups ,the difference of the level of urinary protein , serum albumin, serum cholestero , serum triglyceride, and serum creatinine were not significantly significant before nephropathy model was established(P>0.05).After nephropathy model was established (before treatment),compared with the normal control group, the level of urinary protein , serum cholestero,serum triglyceride, serum creatinine of the other five groups was high(P<0.05),but the level of serum albumin was low(P<0.05). the difference of the level of all above-mentioned index between each two groups among the other five groups was not significantly different(P>0.05) .②After being treated for 6 weeks ,the level of urinary protein ,serum creatinine of the four treatment groups was higher than the model control group ( P < 0.05 ) , so did glomerulosclerosisin dex(GSI) , renal tubulointerstitial lesions , interstitial infiltration of inflammatory cells,the expressions of NF-κBp65 and MCP-1 in renal tissues and the expressions of NF-κBp65mRNA and MCP-1mRNA in renal tissues(P<0.05).The difference in the level of serum cholesterol and triglyceride of the four treatment groups compared with the model control group was not statistically significant(P>0.05).the level of serum albumin of the prednisone group was higher than the model control group(P<0.05),but the difference in the level of serum albumin of the other three treatment groups compared with the model control group was not statistically significant(P>0.05).③After being treated for 6 weeks ,the level of urinary protein , serum reatinine ,GSI,renal tubulointerstitial lesions , interstitial infiltration of inflammatory cells,the expressions of NF-κBp65 and MCP-1,and the xpressionof NF-κB mRNA and MCP-1 mRNA of the other three treatment groups were higher than those in the prednisone group(P<0.05). The difference of the level of above-mentioned index between each two groups among the other three treatment gloups ( except the prednisone group)was not significant(P>0.05). There were no significant difference of the level of serum albumin, cholesterol and triglyceride between each two group among the four treatment gloups(P>0.05).Conclusions:①Different dose of atorvastatin, prednisone and prednisone conbined with high-dose atorvastatin all can reduce proteinuria ,delay the progress of chronic renal failure,mitigate pathological damage of kidney in rats with adriamycin-induced progressive nephropathy.these suggest that atorvastatin and prednison have potential ability of protecting and treating adriamycin-induced progressive nephropathy , which is correlative with inhibiting interstitial infiltration of inflammatory cells , decreasing the expression of NF-κBp65 and MCP-1 in renal tissues.②The above-mentioned protective effects on progressive nephropathy and anti-inflammatory of atorvastatin are independent with dosage and lipid-lowering in six weeks treatment.③Compared with atorvastatin,the renal protective effects and anti-inflammatory of prednisone are strong, but prednisone conbined with high-dose atorvastatin maybe have no synergistic effect of anti- inflammatory and renal protection in six weeks treatment, which reason might be there are competive inhibition between them due to the same acting target of anti- inflammatory or the time of treatment is not long enough.