健脾舒胰汤调控花生四烯酸代谢改善慢性胰腺炎的作用机制OA

Objective To investigate the mechanism of action of Jianpi Shuyi Decoction in regulating arachidonic acid(AA)metabolism in ameliorating dibutyltin dichloride(DBTC)-induced chronic pancreatitis(CP)in rats.Methods A CP model was established in male SD rats through a single tail vein injection of DBTC.Rats were randomly allocated into normal(n=8)and model groups(n=42).On day 2 post-modeling,32 surviving model rats were further randomized into model group,low-Jianpi Shuyi decoction group(L-JPSY group,3.4 g/kg),high-dose Jianpi Shuyi decoction group(H-JPSY group,17 g/kg),and coenzyme Q10(5 mg/kg)group(n=8 each).Treatments were administered once daily by gavage for 3 weeks.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),direct bilirubin(DBIL),and alkaline phosphatase(ALP)were measured using an automated biochemical analyzer,and interleukin(IL)-1β was assessed by enzyme-linked immunosorbent assay.Pancreatic histopathology was evaluated using hematoxylin-eosin(HE)and Sirius red(SR)staining.α-SMA and Col-Ⅰ mRNA and protein expression were detected by RT-qPCR,immunohistochemistry and Western Blot.AA metabolite levels in serum and pancreatic tissues were quantified by LC-MS/MS,and the mRNA expression of key AA metabolic enzymes Ptgs1,Ptgs2,Ptges,Alox5,Alox12,and Alox 15 was analyzed in pancreatic tissues by RT-qPCR.Results Rats in the model group exhibited significantly elevated ALT,AST,TBIL,DBIL,ALP,and IL-1β serum levels compared with rats in the normal group(P＜0.01).Histological examination of pancreatic tissue revealed extensive inflammatory cell infiltration and collagen deposition.α-SMA and Col-Ⅰ mRNA and protein expression were upregulated in pancreatic tissues(P＜0.01).Serum content of the AA metabolites prostaglandin D2(PGD2)and prostaglandin E2(PGE2)were significantly higher in the model group(P＜0.05),while pancreatic tissues showed increases in PGD2,5-hydroxyeicosatetraenoic acid(5-HETE),15-hydroxy eicosatetraenoic acid(15-HETE),and 11(S)-hydroxyeicosatetraenoic acid(11(S)-HETE)(P＜0.01).Ptgs1,Ptgs2,Alox5,and Alox15 mRNA expression was significantly upregulated in pancreatic tissues(P＜0.01).Serum levels of ALT,AST,TBIL,DBIL,ALP,and IL-1β were significantly decreased in the L-JPSY group,H-JPSY group and the coenzyme Q10 group compared with those in the model group(P＜0.05,P＜0.01),and pancreatic inflammation and collagen deposition were alleviated.α-SMA and Col-Ⅰ mRNA and protein expression in pancreatic tissue were significantly reduced(P＜0.05,P＜0.01).L-JPSY group and H-JPSY group significantly reduced serum PGD2 and PGE2(P＜0.05);it also led to reduced pancreatic contents of PGD2,5-HETE,15-HETE,and 11(S)-HETE(P＜0.05,P＜0.01),along with significant downregulation of Ptgs2,Alox5,and Alox15 mRNA expression in pancreatic tissues(P＜0.05,P＜0.01).Conclusions Jianpi Shuyi decoction can significantly inhibit the progression of pancreatic fibrosis in rats with DBTC-induced chronic pancreatitis,with no significant differences between high-and low-doses.Its mechanism of action may be related to the regulation of cyclooxygenase-2 expression in the arachidonic acid pathway and the expression of 5-and 15-lipoxygenase.