Effect and mechanism of pilocarpinein alleviating liver injury induced by acetaminophen(APAP)
Objective To investigate the efficacy and mechanism of pilocarpine in alleviating liver injury in-duced byacetaminophen(APAP).Methods In this study,an acute liver damage model was established u-sing mice that received intraperitoneal injections of APAP.A total of 18 C57BL/6 mice were randomly as-signed to a blank control group,an APAP model group,and a pilocarpine group,with 6 mice in each group.After intraperitoneal administration of pilocarpine(2.5 mg/kg)for 7 days,an APAP acute liver injury model(400 mg/kg)was established 1 hour after the last administration.After 12 hours,blood and liver tissue samples were collected from mice.Evaluate the protective effect of pilocarpine on APAP in-duced liver injury by detecting serum liver function indicators such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),using HE staining method to detect liver pathology and evaluate the pharmacological effect of pilocarpine on APAP induced liver injury.To explore the possible mechanism of liver cell proliferation by detecting proliferating cell nuclear antigen(PCNA)and extracellular protein ki-nase ERK1/2 signaling pathway.Results Compared withblank control group,the levels of ALT and AST in APAP model group mice were significantly increased(P<0.001),indicating the successful establish-ment of the APAP model.Compared with APAP model group,the serum AST content of mice in the pilo-carpine group was significantly reduced(P<0.01),while there was no statistically significant difference in ALT content(P>0.05).The pathological results of HE staining showed that pilocarpine group mice reduced central necrosis of hepatic lobules,intrahepatic hemorrhage,and nuclear pyknosis compared to APAP model group.Western blot results showed that the expression of PCNA protein in liver of mice trea-ted with pilocarpine increased,with a statistically significant difference(P<0.01).The expression of p-ERK/ERK proteins in the pilocarpine group mice wereincreased,and the difference was statistically signif-icant(P<0.01).Conclusion Pilocarpine can alleviate liver damage caused by APAP,and its molecular mechanism may be that pilocarpine promotes liver cell proliferation by activating the m3AchR-ERK1/2 signaling pathway in liver cells.
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