Effect of Modified Shengjiangsan on Renal Fibrosis in Rats with Membranous Nephropathy Based on TLR4/NF-κB Signaling Pathway / 中国实验方剂学杂志

ABSTRACT

Objective:To observe the effect of modified Shengjiangsan on renal fibrosis in rats with membranous nephropathy （MN） and to explore the mechanism of its complications of renal fibrosis. Method:Rats were injected with cationized bovine serum albumin（C-BSA）in the tail vein to establish a rat model of membranous nephropathy. The normal group，model group，modified Shengjiangsan group （27.3 g·kg^-1）and benazepril group（10 mg·kg^-1）were established in this study. Each group was given corresponding dosage of the drug once a day for 4 weeks of continuous intervention. After the administration，we observed the pathological changes of rat kidneys by the technology of Masson staining， silverhexylamine iodate （PASM） staining， transmission electron microscopy （TEM）， immunofluorescence technology （IF） was used to detect immunoglobulin（Ig）G deposition in rat kidneys. The levels of interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， interleukin-6 （IL-6）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA） method. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and immunohistochemistry （IHC） were used to detect the mRNA and protein expression levels of monocyte chemotactic protein 1 （MCP-1）， intercellular adhesion molecule 1 （ICAM-1）， nuclear factor kappa B （NF-<italic>κ</italic>B）， Toll-like receptor 4 （TLR4）， plasminogen activator inhibitor 1 （PAI-1）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMΑ） and type Ⅳ Collagen （Collagen Ⅳ） in rat kidney tissues. Result:Compared with normal group， the kidney tissue of the model group was obviously fibrotic， the serum levels of IL-1<italic>β</italic>， IL-6， and TNF-<italic>α</italic> were significantly increased（<italic>P</italic><0.05）， and the expressions of MCP-1， ICAM-1， NF-<italic>κ</italic>B， TLR4， PAI-1， TGF-<italic>β</italic>₁， <italic>α</italic>-SMA and Collagen Ⅳ mRNA and protein in kidney tissue were significantly increased（<italic>P</italic><0.05）. Compared with model group， modified Shengjiangsan and benazepril significantly improved renal fibrosis in rats， reduced the levels of IL-1<italic>β</italic>， IL-6， and TNF-<italic>α</italic> in the serum of MN rats（<italic>P</italic><0.05）， down-regulated MCP-1， ICAM-1， NF-<italic>κ</italic>B， TLR4， PAI-1， TGF-<italic>β</italic>₁， <italic>α</italic>-SMA and Collagen Ⅳ mRNA and protein expression in kidney tissue（<italic>P</italic><0.05）. Conclusion:Modified Shengjiangsan can reduce the release and expression of inflammatory factors by down-regulating the TLR4/NF-<italic>κ</italic>B signaling pathway， inhibit renal fibrosis， and reduce renal damage in MN rats.