升降散加减方治疗IgAN大鼠作用机制探讨

目的 通过探讨疏通三焦、清热利湿理论指导下的升降散加减方对IgA肾病(immunoglobulin a nephropathy,IgAN)大鼠血清转化生长因子 β1(transforming growth factorβ1,TGF-β1)、白细胞介素-6(interleukin-6,IL-6)、半乳糖缺乏-IgA(ga...

Discussion on the mechanism of Shengjiangsan modified formula in the treatment of IgAN rats

Objective To investigate the possible mechanism of Shengjiangsan modified formula,under the guidance of the theory of dredging sanjiao and clearing heat and promoting diuresis,on transforming growth factor-β1(TNF-β1),interleukin-6(IL-6) and galactokinase deficiency-IgA(Gd-IgA) in serum of immunoglobulin a nephropathy(IgAN) rats.Methods 48 clean grade male SD rats weighing 150 to 180 g were randomly divided into normal group(12 rats) and modeling group(36 rats).After one week of adaptive feeding,the experimental IgA nephropathy rat model was established by gavage combined with bovine serum albumin(BSA),tail vein injection of lipopolysaccharide(LPS),subcutaneous injection of carbon tetrachloride(CCl4) and castor oil.The protocol is as follows:the dose of oral immunogen BSA is doubled compared with the usual dose,600 mg/kg is given by gavage every other day for 6 weeks;The injection method of CCl4 was changed from the previous intraperitoneal injection to subcutaneous injection,with the subcutaneous injection of 0.5 mL castor oil and 0.10 mL CCl4 once a week for 9 weeks,while 0.05 mg LPS was injected into the tail vein at week 6 and 8,respectively.After successfully modeling,the rats in modeling group were randomly divided into Chinese medicine group,western medicine group and model group,12 rats in each group.Chinese medicine group was administrated daily with Chinese medicine concentrated to 1 g/mL water extract,western medicine group was administrated daily with 1.8 mg/kg Benazepril hydrochloride,model group and the normal group both were administrated with the same amount of distilled water once a day for 8 weeks.In this experiment,The 24 hours urinary total protein(24 h-UTP) was detected at week 1,9,15,and 19.The serum creatinine(Scr) and blood urea nitrogen(BUN) and albumin(ALB) of serum in femoral artery blood were detected at week 19.The contents of TGF-β1,IL-6 and GD-IgA in serum were detected by ELISA,and kidney tissues were retained for observation by light microscopy,electron microscopy and immunofluorescence.Results(1) The mental status of rats in Chinese medicine group and western medicine group was better than in model group.(2) Compared with model group,the 24 h-UTP in western medicine group and Chinese medicine group decreased significantly(P<0.05).(3) There was no significant difference among Scr,BUN and ALB in different groups(P>0.05).(4) Compared with model group,the expression intensity of light microscope,electron microscopy and immunofluorescence in western medicine group and Chinese medicine group decreased significantly(P<0.05).(5) The contents of TGF-β1,IL-6 and Gd-IgA in western medicine group and Chinese medicine group decreased significantly than those in the model group(P<0.05).Conclusion Shengjiangsan modified formula,under the guidance of the theory of dredging sanjiao and clearing heat and promoting diuresis,has a therapeutic effect on IgAN rats,and its mechanism of action may be related to the reduction of the contents of TGF-β1,IL-6 and Gd-IgA in serum.