[Animal Modeling] - Lingzhu Tusi Pill Inhibits IKK β/ NF- κ B/MCP-1 pathway reduces adriamycin induced renal proteinuria in rats

  Objective To investigate the effect and mechanism of Lingzhu Tusi Pill on adriamycin induced nephrotic proteinuria.

  Methods 36 male SD rats were included in the experiment. They were randomly divided into 6 groups (6 animals/group). Includes blanks, model groups, and PDTC (NF- κ B inhibitor) group (100 mg/(kg · d), and low, medium, and high dose groups of Lingzhu Tusi Pill (14, 28, 56 g/(kg · d)). All rats except the blank group were induced nephrotic models with adriamycin. After successful modeling, the drug was administered continuously for 6 weeks. Record general vital signs; Collect and detect 24-hour urine protein, plasma albumin (Alb), serum creatinine (Scr), urea nitrogen (BUN), and C-reactive protein (CRP); HE, Masson, PAS staining, and transmission electron microscopy were used to observe the pathological changes of the kidney; Detection of serum IL-6 and TNF by ELISA- α Level; Western Blot detection IKK β/ NF- κ B/MCP-1 pathway related proteins.

  Results The survival status of rats in the model group was poor. Alb decreased and 24-hour urinary protein increased. Extensive swelling of renal tubules and fusion of glomerular foot processes; A large amount of fibers are deposited and the basement membrane is thickened. Serum IL-6, TNF- α And elevated CRP; Kidney p-IKK β、 p-NF- κ B, MCP-1 expression level, and p-IKK β/ IKK β、 p-NF- κ B/ NF- κ The expression of nephrin and podocin decreased with the increase of B ratio (P<0. 05) 05)。 Except for the high-dose group, the rats in the administration group were generally in good condition. Body weight increased, 24-hour urinary protein decreased, and Alb increased. The swelling of renal tubules was reduced, and the fusion of glomerular foot processes was improved. Fibrosis of renal tubules and glomeruli decreased, and basement membrane did not thicken. Serum IL-6, TNF- α And CRP reduction; Kidney p-IKK β、 p-NF- κ B, MCP-1 expression level, and p-IKK β/ IKK β、 p-NF- κ B/ NF- κ The B ratio decreased, and the expression of nephrin and podocin increased (P<0. 05) 05)。

  Conclusion Lingzhu Tusi Pill can reduce 24-hour urinary protein and serum inflammatory factors in rats with adriamycin induced nephropathy, and its mechanism may be related to the inhibition of IKK β/ NF- κ B/MCP-1 signal pathway.