Effect of Polysaccharides from Plantaginis Semen on Renal Injury and Gut Microbiota in Rats with Membranous Nephropathy / 中国实验方剂学杂志

ABSTRACT

Objective:To study the protective effect of polysaccharides from Plantaginis Semen （PSP） against renal injury in rats with membranous nephropathy （MN） and its influence on the gut microbiota to provide a theoretical basis for the further investigation of PSP in the treatment of MN. Method:The MN model was induced by tail vein injection of cationic bovine serum albumin （C-BSA， 3.5 g·L^-1） in rats with a modeling period of seven weeks. At the 4th week of modeling， the model rats were divided into a model group， a positive drug group （benazepril hydrochloride， 10 mg·kg^-1·d^-1）， a PSP high-dose group （PSP-H， 800 mg·kg^-1·d^-1）， a PSP medium-dose group （PSP-M， 400 mg·kg^-1·d^-1）， and a PSP low-dose group （PSP-L， 200 mg·kg^-1·d^-1） according to the random number table， with 10 in each group. Ten healthy rats were assigned to the normal control group. The rats in the normal control group and the control group received an equal amount of physiological saline by gavage， and those in the groups with drug intervention were administered correspondingly，once a day，for consecutive four weeks. The pathological changes of rat kidney and colon tissues were observed by optical microscopy. The enzyme-linked immunosorbent assay （ELISA） was used to detect the content of tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>） and interleukin-1<italic>β </italic>（IL-1<italic>β</italic>） in the serum and colon tissues. The immunohistochemistry （IHC） was used to detect the protein expression of TNF-<italic>α </italic>and IL-1<italic>β </italic>in renal tissues. The 16S rRNA sequencing method was used to investigate the effect of PSP on the gut microbiota in MN rats. Result:Compared with the normal control group， the model group showed enlarged glomeruli， thickened basement membrane， atrophied colonic gland， increased TNF-<italic>α</italic> and IL-1<italic>β</italic> in the serum and colon tissues （<italic>P</italic><0.05）， and elevated protein expression of TNF-<italic>α</italic> and IL-1<italic>β </italic>（<italic>P</italic><0.01）. Compared with the model group， the positive drug group and the PSP-H group displayed shrunk glomerular capsules， relieved basement membrane thickening， and neatly arranged colonic mucosa in colon tissues， while the PSP-M and PSP-L groups were inferior in improving renal tissues and colon tissues. Additionally， the PSP-H and PSP-M groups showed declining TNF-<italic>α</italic> and IL-1<italic>β</italic> in the serum and colon tissues （<italic>P</italic><0.05） and dwindled protein expression of TNF-<italic>α</italic> and IL-1<italic>β </italic>in the renal tissues （<italic>P</italic><0.01）. No significant difference was observed in the PSP-L group. Compared with the normal control group， the model group showed increased abundance of Firmicutes and decreased abundance of Bacteroidetes. After PSP intervention， the abundance of Firmicutes was decreased， while that of Bacteroidetes was increased， and such changes were predominant in the PSP-H group. Conclusion:PSP can effectively alleviate renal injury， reduce the expression of inflammatory factors， regulate the structure of gut microbiota， and improve the damaged intestinal barrier of MN rats.