加味沙参麦冬汤调节EGFR/MAPK信号通路对慢性萎缩性胃炎大鼠的保护作用研究

Effect of modified Shashen Maidong Decoction on rats with chronic atrophic gastritis by regulating EGFR/MAPK signaling pathway

目的观察加味沙参麦冬汤对慢性萎缩性胃炎(CAG)模型大鼠的治疗作用,并通过EGFR/MAPK信号通路探讨其作用机制。方法60只SPF级Wistar大鼠按体质量随机分为空白组、模型组、阳性对照组、加味沙参麦冬汤低、中、高剂量组,每组10只。以维酶素作为阳性对照药,空白组正常饲养,其余各组大鼠自由饮用甲基硝基亚硝基胍(MNNG)溶液建立CAG模型。造模成功后,阳性对照组给予维酶素(0.3 g/kg)灌胃治疗,加味沙参麦冬汤低、中、高剂量组分别给予不同剂量(4.84、9.68、19.35 g/kg)灌胃,每日1次,持续12周。检测各组大鼠胃黏膜血流量,HE染色观察大鼠胃黏膜组织病理学变化,ELISA检测血清GAS、SS、MTL水平,Western-blot检测胃黏膜组织中ERF、EGFR、ERK1/2及p-ERK1/2的蛋白表达,RT-PCR检测ERF、EGFR、p-ERK1/2的mRNA表达。结果与空白组比较,模型组大鼠胃黏膜血流量显著降低(P<0.01),胃黏膜可见炎性细胞浸润,胃腺数量明显减少,腺体萎缩,血清GAS、SS水平均显著降低,MTL水平明显升高(P<0.01),胃黏膜组织中ERF、EGFR、p-ERK1/2蛋白和mRNA表达均明显增多(P<0.01)。加味沙参麦冬汤低、中、高剂量组随给药剂量的增加,大鼠胃黏膜血流量较模型组明显升高(P<0.05,P<0.01),胃黏膜慢性炎症及萎缩程度逐渐改善,明显升高了血清GAS、SS水平,降低了MTL水平(P<0.05,P<0.01),同时显著下调了胃黏膜组织中ERF、EGFR、p-ERK1/2蛋白和mRNA表达(P<0.05,P<0.01)。结论加味沙参麦冬汤可增加CAG大鼠胃黏膜血流量,调节胃肠激素分泌,明显改善大鼠胃黏膜病变,其机制可能与抑制EGFR/MAPK信号通路的异常激活相关。

Objective To observe the therapeutic effect of modified Shashen Maidong Decoction on chronic atrophic gastritis(CAG)model rats,and to explore its mechanism based on the EGFR/MAPK signaling pathway.Methods A total of sixty SPF Wistar rats were randomly divided into a blank group,a model group,a positive control group,and low-,medium-and high-dose groups of modified Shashen Maidong Decoction according to their body weight,with 10 rats in each group.Taking vermin as the positive control drug,the blank group was fed normally,while the other groups were given free access to methylnitrosoguanidine(MNNG)solution to establish the CAG model.After the model was successfully established,the positive control group was given vitrein(0.3 g/kg)by intragastric administration,while the low-,medium-and high-dose groups of modified Shashen Maidong Decoction were given different doses(4.84,9.68,19.35 g/kg)by gavage respectively,once a day for 12 weeks.The blood flow gastric mucosal was detected in each group,and the pathological changes of gastric mucosal tissues were observed by HE staining,while the levels of GAS,SS and MTL in serum were detected by ELISA,and the protein expressions of ERF,EGFR,ERK1/2 and p-ERK1/2 in the gastric mucosal tissues were detected by Western-blot,while the mRNA expressions of ERF,EGFR and p-ERK1/2 were detected by RT-PCR.Results Compared with the blank group,the blood flow of gastric mucosa was significantly decreased in the model groups(P<0.01),and the in?ammatory cell in?ltration was observed in the gastric mucosa,while the number of gastric glands was signi?cantly reduced with the glands atrophy,and the levels of serum GAS and SS were significantly decreased,while the level of MTL was significantly increased(P<0.01),and the protein and mRNA expressions of ERF,EGFR and p-ERK1/2 in the gastric mucosa were signi?cantly increased(P<0.01).With the increase of dosage,the blood flow of gastric mucosa in the low-,medium-and high-dose groups of modified Shashen Maidong Decoction was significantly increased than that in the model group(P<0.05,P<0.01),and the chronic inflammation and atrophy of gastric mucosa were gradually improved,with the levels of serum GAS and SS being significantly increased,while the level of MTL being decreased(P<0.05,P<0.01),and the protein and mRNA expressions of ERF,EGFR and p-ERK1/2 in gastric mucosa being significantly down-regulated(P<0.05,P<0.01).Conclusion Modified Shashen Maidong Decoction can increase the blood flow of gastric mucosa,regulate the secretion of gastrointestinal hormones,and significantly improve the gastric mucosal lesions in CAG rats,whose mechanism may be related to inhibiting the abnormal activation of the EGFR/MAPK signaling pathway.