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Study of Compound Shelong Capsules on inhibiting Bax/Caspase-3 signaling pathway and reducing apoptosis in renal tissues of rats with membranous nephropathy |
JIA Shiyan1 ZHONG Qiming2 SI Ruihua1 FAN Xiaoyang2 YAN Wenyun1 LIU Guangzhen2 |
1.Shanxi University of Chinese Medicine, Shanxi Province, Jinzhong 030619, China;
2.Shanxi Institute of Traditional Chinese Medicine, Shanxi Province, Taiyuan 030012, China |
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Abstract Objective To investigat the effect of Compound Shelong Capsules on inhibiting Bax/Caspase-3 signaling pathway and reducing apoptosis in renal tissues of rats with membranous nephropathy. Methods Ten SPF male SD rats aged six weeks were selected as normal group, and the other 40 rats were injected with cationic bovine serum albumin (Alb) to construct the rat model of membranous nephropathy. They were divided into model group, Tripterygium Wilfordii Polyglycoside Tablets group, Compound Shelong Capsules low-dose and high-dose groups, with 10 rats in each group by random number table method. Except normal group and model group were given the same amount of normal saline, other groups were given the corresponding drug intragastric administration for four weeks. HE staining, Masson staining, transmission electron microscopy, and scanning electron microscopy were used to observe the pathological changes of renal tissues in each group; the contents of urinary microalbumin (mAlb), serum creatinine (SCr), triglyceride (TG), total cholesterol (TC), Alb, and total protein (TP) were compared among all groups; the apoptosis rate of renal tissues cells in each group was compared; the expression levels of Nephrin, Podocin, Bcl-2, Bax, and Caspase-3 mRNA in renal tissues of all groups were compared. Results Compared with normal group, the content of urinary mAlb in model group was increased (P<0.05); the contents of serum Alb and TP were decreased, while the contents of TC, TG, and SCr were increased (P<0.05). Compared with model group, the contents of urinary mAlb in Compound Shelong Capsules low-dose and high-dose groups was decreased (P<0.05); the contents of serum Alb and TP were increased, while the contents of TC, TG, and SCr were decreased (P<0.05). Compared with Compound Shelong Capsules low-dose group, the content of urinary mAlb in Compound Shelong Capsules high-dose group was decreased (P<0.05); the contents of serum Alb and TP were increased, while SCr was decreased (P<0.05). In the normal group, the structure of glomeruli was intact by HE staining; but no tissue fibrosis was observed by Masson staining. In model group, HE staining showed increased glomerular volume and vacuolar degeneration of renal tubules, accompanied by protein tubule type; Masson staining showed tissue fibrosis and blue collagen fiber tissue. Compared with model group, glomerular volume increased, tubular vacuolar degeneration and tissue fibrosis decreased in Compound Shelong Capsules low-dose and high-dose groups. In normal group, the structure of basement membrane was intact, and the structure of podocytes was normal; in model group, the glomerulus was edema, the basement membrane thickened, the foot process fused and widened, the structure of podocytes was seriously damaged, and cytoskeletal proteins were exposed; compared with model group, basilar membrane thickening was reduced and podocyte morphology and structure tended to be normal in Compound Shelong Capsules low-dose and high-dose groups. Compared with normal group, the apoptosis rate of renal tissues cells in model group was increased (P<0.05); compared with model group, the apoptosis rate of renal tissues cells in Compound Shelong Capsules low-dose and high-dose groups was decreased (P<0.05); compared with Compound Shelong Capsules low-dose group, the apoptosis rate of renal tissues in Compound Shelong Capsules high-dose group was decreased (P<0.05). Compared with normal group, the expression levels of Nephrin, Podocin, and Bcl-2 mRNA in model group were decreased, the expression levels of Caspase-3 and Bax mRNA were increased, and Bcl-2/Bax ratio was decreased (P<0.05). Compared with model group, the expression levels of Nephrin, Podocin, and Bcl-2 mRNA in Compound Shelong Capsules low-dose and high-dose groups were increased, the expression levels of Caspase-3 and Bax mRNA were decreased, and Bcl-2/Bax ratio was increased (P<0.05). Compared with Compound Shelong Capsules low-dose group, the expression levels of Nephrin and Podocin mRNA in Compound Shelong Capsules high-dose group were increased, while Bcl-2/Bax ratio was increased (P<0.05). Conclusion Compound Shelong Capsules can effectively improve albuminuria in rats with membranous nephropathy, significantly reduce renal pathological injury, and delay the progression of membranous nephropathy, the mechanism of which may be related to the inhibition of podocyte apoptosis.
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