Ligustilide Improves LPS-Induced Renal Podocyte Injury in Mice by Inhibiting RhoA/ROCK Signaling Pathway
Objective To investigate the improvement effect and mechanism of ligustilide on lipopolysaccharide(LPS)-induced renal podocyte injury in mice.Methods(1)In vivo experiment:the mice were randomly divided into blank control group,LPS induction group,ligustilide low-and high-dose groups,ligustilide high-dose+pcDNA-NC(RhoA negative control)group,ligustilide high-dose+pcDNA-RhoA(RhoA overexpression)group.Except for the blank control group,mice in other groups were subjected to LPS-induced acute kidney injury(AKI)model.After the intervention,the levels of blood urea nitrogen(BUN)and creatinine(Cr)in the serum of mice were detected,the pathological changes of kidney tissue in mice were observed by periodic acid-schiff(PAS)staining,and the protein expressions of RhoA and Rho-associated coiled-coil forming protein kinase(ROCK)in kidney tissue were detected by Western Blot.(2)In vitro experiments:the cultured mouse podocyte MPC5 was divided into blank control group,LPS induction group,ligustilide low-and high-dose groups,ligustilide high-dose+pcDNA-NC group,ligustilide high-dose+pcDNA-RhoA group.Cell count kit 8(CCK-8)method was used to detect the proliferation activity of podocytes,flow cytometry was used to detect apoptosis,phalloidin staining method was used to analyze cytoskeleton,and Western Blot was used to detect the expressions of RhoA and ROCK proteins in the cells.Results Compared with the blank control group,the levels of BUN and Cr in serum,renal tissue injury score,and the protein expressions of RhoA and ROCK in the LPS-induced group were increased(P＜0.05).Compared with the LPS-induced group,the levels of BUN and Cr in serum,renal tissue injury score,and the expression levels of RhoA and ROCK in the low-and high-dose ligustilide groups were decreased(P＜0.05).Compared with the blank control group,the cell proliferation activity,F-actin fluorescence intensity,RhoA and ROCK expressions in the LPS-induced group were decreased(P＜0.05),and the apoptosis rate was increased(P＜0.05).Compared with the LPS-induced group,the cell proliferation activity,F-actin fluorescence intensity,RhoA and ROCK expressions were increased(P＜0.05),and the apoptosis rate was decreased in the low-and high-dose ligustilide groups(P＜0.05).Overexpression of RhoA reversed the alleviation effect of ligustilide on LPS-induced renal tissue and podocyte injury in mice(P＜0.01).Conclusion Ligustilide may improve LPS-induced renal podocyte injury in mice by inhibiting RhoA/ROCK signaling pathway.
ligust lideacute kidney injuryRhoA/Rho-associated coiled-coil-forming protein kinase(ROCK)pathwaylipopolysaccharidepodocytesmice
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