OBJECTIVE: To investigate the protective effects of andrographolide on membranous nephropathy（MN） in rats. METHODS: Eighty clean healthy male SD rats were divided into the normal group

model group

andrographolide group（andrographolide 50 mg/kg） and benazepril group（benazepril hydrochloride 10 mg/kg）

with 20 rats in each group. Rats in the model group

andrographolide group

benazepril group were injected with cationized bovine serum albumin through the tail vein to replicate the MN rat model. The andrographolide group and benazepril group were given intragastric administration once a day for four consecutive weeks. The normal group and model group were given 0.9% sodium chloride solution by gavage once a day for four consecutive weeks. The renal function indicators were detected by biochemical analysis method. Histopathological examination of renal tissue was performed by Hematoxylin-Eosin staining and Masson staining

and ultrastructural changes of renal tissue were observed by transmission electron microscopy（TEM）. The contents of tumor necrosis factor-α（TNF-α）

interleukin-6（IL-6）

intercellular adhesion molecule-1（ICAM-1） were detected by enzyme-linked immunosorbent assay（ELISA） method

the expression of proteins were detected by Western blot. RESULTS: Compared with the model group

the renal tissue lesions and ultrastructural lesions in the andrographolide group and benazepril group decreased significantly

and the effect of the andrographolide group was more significant; the 24 h urine protein quantification and creatinine（SCr） levels decreased significantly; the contents of TNF-α

IL-6 and ICAM-1 decreased significantly; the expressions of Toll-like receptor 4（TLR4）

nuclear factor κB（NF-κB）

transforming growth factor β1（TGF-β1）

phosphorylated Smad2 and phosphorylated Smad3

collagen type Ⅰ and type Ⅲ decreased significantly

and the differences were statistically significant（P<0.01）. The above indicators in the andrographolide group were significantly better than those in the benazepril group

with statistically significant differences（P<0.05 or P<0.01）. CONCLUSIONS: Andrographolide has an inhibitory effect on renal fibrosis in MN rats

which may be related to the inhibition of TLR4/NF-κB pathway and TGF-β1/Smad pathway

reduction of inflammatory response and extracellular matrix production.