五丹胃福颗粒对胃癌前病变大鼠PI3K/Akt信号通路影响的实验研究

Experimental Study on Effect of Wudan Weifu Granules(五丹胃福颗粒)on PI3K/Akt Signal Pathway in Rats with Gastric Precancerous Lesion

目的 基于PI3K/Akt信号通路,探讨五丹胃福颗粒干预胃癌前病变(PLGC)大鼠的机制。方法 采用改良MNNG+复合法,造模成功PLGC大鼠,分为模型组(A组)、中药(五丹胃福颗粒)低剂量组(B组)、中药中剂量组(C组)、中药高剂量组(D组)、理气组(E组)、祛瘀组(F组)、叶酸组(G组)共7组进行观察,检测COX-2、eNOS、NF-КB、PI3K、Akt等指标。结果 COX-2:治疗12周,D组、E组、F组、G组与A组比较,COX-2表达减少(P<0.05);B组、C组与A组比较,COX-2表达减少,但差异没有统计学意义(P>0.05)。E组、F组与D组比较,没有统计学意义(P>0.05)。E组与F组比较,差异没有统计学意义(P>0.05)。eNOS:治疗12周,胃窦部黏膜D组、E组、F组、G组与A组比较,eNOS显著降低(P<0.05)。B组、C组与A组比较,表达明显减少,但差异没有统计学意义(P>0.05)。E组、F组与D组比较,没有统计学意义(P>0.05)。E组与F组比较,没有统计学意义(P>0.05)。NF-κB:胃窦部D组、E组、F组、G组与A组比较,NF-κB显著降低(P<0.05)。B组、C组与A组比较,表达明显减少,但差异没有统计学意义(P>0.05)。E组、F组与D组比较,没有统计学意义(P>0.05)。E组与F组比较,没有统计学意义(P>0.05)。PI3K:治疗12周,B组、C组、D组、E组、F组、G组与A组比较,PI3K表达阳性率减少,D组有统计学意义(P<0.05),其余治疗组(P<0.05)。B组,C组与D组比较,差异有统计学意义(P<0.05)。E组、F组与D组比较(P<0.05)。Akt:治疗12周,B组、C组、D组、E组、F组、G组与A比较,Akt表达阳性率减少,D组及G组有统计学意义(P<0.05),余治疗组(P<0.05)。B组,C组与D组比较,差异有统计学意义(P<0.05)。E组、F组与D组比较,差异有统计学意义(P<0.05)。结论 五丹胃福颗粒通过影响PLGC大鼠PI3K/Akt信号通路而降低eNOS、NF-КB、COX-2的表达,从而延缓PLGC向胃癌的发展。

Objective Based on the PI3 K/Akt signaling pathway,to explore the mechanism of Wudan Weifu Granules(五丹胃福颗粒)intervention in rats with gastric precancerous lesions(PLGC).Methods The modified MNNG+compound method was used to successfully model PLGC rats,which were divided into model group(group A),low-dose Chinese medicine(Wudan Weifu Granules)group(group B),middle-dose Chinese medicine group(group C),high-dose Chinese medicine group(D group),Qi-regulating group(E group),blood stasis-resolving group(F group),and folic acid group(G group).Cyclooxygenase-2(COX-2),endothelial nitric oxide synthase(NOS),nuclear factor kB(NF-kB),phosphoinositide-3-kinase(PI3 K)and aminothreonine protein kinase(Akt)were detected.Results COX-2:After treatment for 12 weeks,the expression of COX-2 was decreased in group D,E,F and G compared with that of group A(P<0.05).Compared with group A,group B and C showed a significant decrease in expression,but the difference was not statistically significant(P>0.05).There was no statistical significance among group E,group F or group D(P>0.05).There was no statistically significant difference between group E and group F(P>0.05).eNOS:After treatment for 12 weeks,eNOS in the gastric antrum mucosa in group D,E,F and G showed a significant decrease compared with that in group A(P<0.05).Compared with group A,group B and group C showed a significant decrease in expression,but the difference was not statistically significant(P>0.05).There was no statistical significance among group E,group F or group D(P>0.05).There was no statistical significance between group E and group F(P>0.05).NF-κB:Compared with that of group A,NF-κB in gastric antrum of group D,E,F and G was decreased significantly(P<0.05).Compared with that of group A,the expression of group B and group C was significantly reduced,but the difference was not statistically significant(P>0.05).There was no statistical significance among group E,group F and group D(P>0.05).There was no statistical significance between group E and group F(P>0.05).PI3 K:After treatment for 12 weeks,the positive rates of PI3 K expression of group B,C,D,E,F and G were decreased compared with that of group A and that of the D group was statistically significant(P<0.05),and that of the other treatment groups were not significant(P>0.05).Compared with that of group D,the expressions of group C and group B had statistically significant difference(P<0.05).Compared with that of group D,the expressions of group F and group E were statistically significant(P<0.05).Akt:After treatment for 12 weeks,the positive rates of Akt expression in group B,C,D,E,F and G were decreased compared with that of group A.There was statistical significance in group D and G(P<0.05),and the rest groups had no significant difference(P>0.05).Compared with that of group D,the expressions of group B and C were statistically significant(P<0.05).Compared with that of group D,the expressions of group E and group F were statistically significant(P<0.05).Conclusion Wudan Weifu Granules can reduce the expressions of eNOS,NF-КB and COX-2 by affecting the PI3 K/Akt signaling pathway in PLGC rats,thereby delaying the development of PLGC to gastric cancer.