基于干细胞生长因子/酪氨酸激酶受体信号通路探讨红芪多糖治疗糖尿病胃轻瘫大鼠的作用

Study on the effects of hedysarum polysaccharide on diabetic gastroparesis based rats on stem cell growth factor-tyrosine kinase receptor signaling pathway

目的 探究红芪多糖(HPS)改善糖尿病胃轻瘫(DGP)大鼠胃动力的作用和可能机制。方法 将60只SPF级健康雄性Wistar大鼠随机分为空白组(常规饲养)、模型组(构建DGP模型)、对照组(DGP模型+3.5 mg·kg^(-1)枸橼酸莫沙必利溶液灌胃)、低、中、高剂量实验组(DGP模型+按50、100和200 mg·kg^(-1)给予HPS灌胃),每组10只大鼠,每日1次,连续8周。用免疫组化法测定大鼠胃窦组织中Cajal间质细胞(ICC)的含量,用实时荧光定量聚合酶链反应法检测大鼠胃窦组织中干细胞生长因子(SCF)和酪氨酸激酶受体(c-kit)mRNA的表达水平。结果 空白组、模型组、对照组和中、高剂量实验组大鼠胃窦组织中ICC含量的阳性面积分别为(2 537.00±372.89)、(254.99±139.80)、(2 270.00±132.84)、(1 339.00±218.05)和(1 530.00±242.56)μm^(2),SCF mRNA表达水平分别为1.02±0.28、0.24±0.03、3.51±0.70、2.23±0.22和3.37±0.13,c-kit mRNA表达水平分别为1.00±0.07、0.18±0.02、2.29±0.42、1.88±0.36和2.14±0.33。与模型组比较,中、高剂量实验组及对照组的上述指标差异均有统计学意义(均P<0.01)。结论 HPS可改善胃动力,促进胃排空,其机制可能与上调DGP大鼠胃窦组织中SCF/c-kit信号通路的表达、提高ICC的含量,从而达到对DGP的治疗效果。

Objective To investigate the role and possible mechanism of hedysarum polysaccharide(HPS)in improving gastric motility in diabetic gastroparesis(DGP)rats.Methods Sixty SPF healthy male Wistar rats were divided into blank group(regular),model group(constructing DGP model),control group(DGP model+3.5 mg·kg^(-1) mosapride citrate solution for gastric gavage),experimental-L,-M,-H groups(DP model+50,100,200 mg·kg^(-1) HPS solution for gastric gavage),10 rats in each group,once a day for eight weeks.Immunohistochemistry was used to determine the expression of interstitial cells of Cajal(ICC)in rat gastric antral tissue.Real-time polymerase chain reaction was used to detect the mRNA expression levels of stem cell growth factor(SCF)and tyrosine kinase receptor(c-kit)genes in rat gastric antral tissue.Results The positive areas of ICC contents in rat gastric antral tissues of the blank group,model group,control group and experimental-M,-H groups were(2537.00±372.89),(254.99±139.80),(2270.00±132.84),(1339.00±218.05)and(1530.00±242.56)μm^(2);the mRNA expression levels of SCF gene were 1.02±0.28,0.24±0.03,3.51±0.70,2.23±0.22 and 3.37±0.13;the mRNA expression levels of c-kit gene were 1.00±0.07,0.18±0.02,2.29±0.42,1.88±0.36 and 2.14±0.33,respectively.Compared with the model group,the differences of above indexes in the experimental-M,-H groups and control group were all statistically significant(all P<0.01).Conclusion HPS can improve the gastric motility and promote the gastric emptying,and its mechanism may be related to up-regulating the expression of SCF/c-kit signaling pathway and increasing the content of ICC,thus achieving the therapeutic effect on DGP.