The Effect And Mechanism Of Dachaihu Decoction On MAPK Signaling Pathway Of Pancreas With Chronic Pancreatitis In Mice

【Objective】To observe the role of MAPK signaling pathway in thedevelopment of Chronic Pancreatitis and the effect of DaChaiHu Decoctionon the pancreatic fibrosis.【Methods】Healthy male Kunming mouse were randomly divided into threegroups(n=90): Control group、 Chronic Pancreatitis group、 DaChaiHuDecoction group。Disposable mouse tail vein injection of DBTC (8mg/kg),joint with10%ethanol drinking to induced model of chronic pancreatitis, Three days later, the mouses were randomly divided into model group andDachaihutang treatment group. The treatment group received Dachaihutang(0.5g crude drug/ml,6g/kg/d)) administered treatment. The control groupreceived no treatment, a normal diet as control. ether anesthesia animalsat four time points(1、2、4、8weeks), HE staining and collagen fibers(Masson) staining to observe the histopathological changes on pancreas. Serum AMS and HA content were measured according to the kit method. totalRNA and protein was extracted, RT-PCR detect the content of matrixmetalloproteinases (MMP) and tissue inhibitor of metalloproteinaseinhibitors (TIMP); Blot-western detect a collagen (Collagen I, colA1) andthe phosphorylation of MAPK (P-ERK, P-JNK, P-p38).【Results】1.One day after DBTC injection the pancreas presenting with acuteinflammation and the mainly inflammatory cells were neutrophils;After oneweek macrophage infiltration were increased, fat necrosis were visible and the pancreatic acini showed varying degrees of necrosis, pancreatic tissue of2w group showed interstitial edema, infiltration ofinflammatory cell has increased, small focal necrosis were visible in partof acinar. Compared with2w,4w group showed more serious structuraldamage on the pancreas, and significant fibrosis were occurs. Thestructural damage of pancreatic tissue and fibrosis in8w group were themost serious, pancreatic acinar atrophy, the pancreas showed a seriousfibrosis change. Collagen fibers (Masson) staining demonstrated thatfibroblasts appear after1w, pancreatic tissue showed interstitial edemaafter2w;4w later the fibrosis were obviously, the acinar atrophied, theoriginal structure of lobular were damaged; after8w the pancreas showedsignificant fibrosis, pancreas tissue is severely divided by fibrous. Accompanied with inflammation and fibrosis, serum AMS, HA content werecontinued increased, there was a significant difference compared with thecontrol group(P<0.01).the content of MMP-1、colA1、P-ERK、P-JNK、P-p38in model group were all increased.2. Compared with the same time point in the model group, The HEstaining and collagen fibers (Masson) staining of Dachaihu treatmentgroup displayed that the inflammation were relieved, and the level offibrosis were significantly reduced. With prolonged of treatment, thepancreatic serum AMS, HA content of Dachaihu Decoction group weredecreased. The expression of MMP-1in pancreatic tissue were also declined;the phosphorylation of MAPK and colA1were reduced.【Conclusion】1. CP model can be induced by DBTC intravenous injection joint withalcohol drinking. MAPK signaling pathway is related to the developmentof chronic pancreatitis and a therapeutic target for pancreaticfibrosis. 2. The mechanism of Dachaihu Decoction on chronic pancreatitis is relatedto regulating the MAPK signaling pathway.