| Object: To explore the molecular mechanism of Banxia Xiexin Decoction based on MAPK/ERK signaling pathway in intervening precancerous lesions in rats,and to compare the effect differences between different doses of Banxia Xiexin Decoction,so as to provide scientific basis for clinical application and in-depth research.Methods:(1)The PLGC rat model was established by MNNG gavage in SPF Wistar male young rats.After the model was successfully prepared,the model group was divided into the model group,the low-dose group and the high-dose group according to the random number table method.After the experiment,pathological development of gastric mucosa in each group was observed by HE staining.(2)Elisa,Western blot and immunohistochemistry were used to detect the protein of key targets of cell proliferation factors c-fos,Kras and MAPK/ERK signaling pathway.Serum EGFR content was observed by Elisa.The m RNA expressions of factors in c-Jun,JNK and MAPK/ERK pathway in gastric mucosa were observed by PCR.Results:(1)Histopathological findings showed that the high-dose group of Banxia Xiexin Decoction could more effectively reduce the infiltration of inflammatory cells and mucosal congestion in the gastric submucosa of rats with precancerous lesions,and had a better recovery effect on the reduction and atrophy of intrinsic glands in the gastric mucosa.(2)Elisa and PCR results showed that,compared with model group,the heart of this decoction soup both high and low dose group can significantly reduce serum c--Fos,EGFR and protein expression of Kras cut in gastric mucosa(P < 0.01),and c-Fos,c--jun and raised JNK m RNA(P < 0.05),Western blot results showed that Banxia Xiexin Decoction group could reduce the content of c-fos protein,immunohistochemical results showed that this decoction high and low dose group can cut c-Fos,Kras protein expression.(3)The detection of MAPK/ERK pathway indicators in the laboratory showed that the protein and gene expression levels of Raf-1,MEK,p-MEK,ERK,p-ERK and Elk-1 in high and low doses could be effectively down-regulated.(4)Compared with low dose group,high dose group can be more effective in PCR gene detects cut ERK in gastric mucosa,Elk-1,MEK m RNA(P < 0.05)expression,combining Westernblot results show that compared with low dose group of this decoction heart decoction high dose group can more effectively cut,MEK,ERK1,Raf-1 protein expression,Immunohistochemical analysis showed that the protein expressions of c-Fos,p-MEK(P < 0.01),Kras and MEK(P < 0.05)in the high-dose group of Banxia Xiexin Decoction were more effective than those in the low-dose group.Conclusion:(1)Banxia Xiexin Decoction can reduce the inflammatory infiltration in the gastric submucosa of PLGC rats,and effectively improve the atrophy of the inherent glands in the gastric mucosa,and reduce the intestinal metaplasia.(2)Banxia Xiexin Decoction can inhibit the abnormal activation of Kras,c-Fos c-Jun and other proto-oncogenes,promote the expression of JNK protein gene,break the imbalance of cell proliferation and apoptosis of gastric mucosal injury,alleviate the development of the disease,and prevent the further development of gastric mucosal injury.(3)heart soup this decoction can inhibit the MAPK/ERK signaling pathway,MEK,key factor Raf-1 p-MEK,ERK,p-ERK,Elk-1,such as the abnormal activation of,thus inhibiting gastric mucosa epithelial cells and inherent cells proliferation and accelerate its apoptosis,prevent gastric mucosa epithelium cells and lamina propria cancerous changes may be this decoction heart is one of the important mechanisms of soup treating PLGC.(4)Compared with model group,Banxia Xiexin Decoction low-dose group could inhibit the abnormal activation of key targets of MAPK/ERK signaling pathway,maintain the balance of cell proliferation and apoptosis,and improve gastric mucosal pathology,but combined with the general situation of rats,pathological tissue mucosal manifestations and laboratory indicators,the effect of high-dose group was stronger than that of Banxia Xiexin Decoction low-dose group. |
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