化瘀通便汤对慢传输型便秘大鼠PI3K/Akt/eNOS信号通路及血管活性肽的影响

Effect of Huayu Tongbian Decoction(化瘀通便汤)on PI3K/Akt/eNOS Signaling Pathway and Vasoactive Peptide in Rats with Slow Transit Constipation

目的:研究化瘀通便汤对磷脂酰肌醇3激酶/蛋白激酶B/内皮型一氧化氮合酶(PI3K/Akt/eNOS)信号通路及血管活性肽(VIP)的影响,探讨该方药对慢传输型便秘大鼠的治疗机制。方法:90只大鼠随机抽取15只为正常组,其余75只按复方地芬诺酯灌胃造模法制造慢传输型便秘模型,根据简单随机抽样方法分为5组(模型组、化瘀通便汤低剂量组、化瘀通便汤中剂量组、化瘀通便汤高剂量组、麻仁软胶囊组),每组15只。化瘀通便汤低、中、高剂量组分别予化瘀通便汤24 g/(kg·d)、48 g/(kg·d)、96 g/(kg·d)灌胃。麻仁软胶囊组用常温蒸馏水调配麻仁软胶囊至2.4 g/mL,灌胃量为20 mL/(kg·d)。模型组与正常组均与等量常温蒸馏水进行灌胃,日1次。各组干预2周后,检测大鼠首次排黑便时间、粪便含水率及结肠组织磷酸化蛋白激酶B(P-Akt)阳性细胞、VIP、一氧化氮(NO)、内皮型一氧化氮合酶(eNOS)水平。结果:与模型组比较,化瘀通便汤各组及麻仁软胶囊组均能缩短大鼠首次排黑便时间,增加大鼠粪便含水率,提高大鼠结肠组织P-Akt含量、P-Akt阳性细胞水平,降低VIP的表达,降低结肠组织中NO及eNOS的含量(P<0.05);与麻仁软胶囊组比较,化瘀通便汤低剂量组与麻仁软胶囊组相近(P>0.05),化瘀通便汤中、高剂量组明显优于麻仁软胶囊组(P<0.05)。结论:化瘀通便汤可通过调控PI3K/Akt/eNOS信号通路及VIP表达,对慢传输型便秘大鼠起治疗作用。

Objective:To explore the mechanism of Huayu Tongbian Decoction(化瘀通便汤)on rats with slow transit constipation by observing the effect of the decoction on phosphoinositide 3 kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)signaling pathway and vasoactive peptide(VIP).Methods:A total of 15 rats were randomly selected from 90 rats as the normal group,and the remaining 75 rats model of slow-transport constipation were made by the compound diphenoxylate gavage.According to a simple random sampling method,they were divided into 5 groups[model group,low-dosage group of Huayu Tongbian Decoction,medium-dosage group of Huayu Tongbian Decoction,high-dosage group of Huayu Tongbian Decoction,and Maren Soft Capsule(麻仁软胶囊)group],15 rats in each group.The low,medium and high doses of Huayu Tongbian Decoction were administered by gavage of 24 g/(kg·d),48 g/(kg·d),96 g/(kg·d)to the low,medium and high dosage group of Huayu Tongbian Decoction respectively.In Maren Soft Capsule group:at normal temperature,distilled water was mixed with Maren Soft Capsule to 2.4 g/mL,and the intragastric amount was 20 mL/(kg·d).In model group and normal group:both were given intragastrically with equal amount of room temperature distilled water once a day.After 2 weeks of treatment in the six groups of rats,the time of first black stool,water content of feces,phosphorylated protein kinase B(P-Akt)content in colon tissue,P-Akt positive cell level,VIP content and the content of nitric oxide(NO)and endothelial nitric oxide(eNOS)in colon tissues were examined.Results:Each group of Huayu Tongbian Decoction and Maren Soft Capsule group can shorten the time of first black stool,increase the water content of feces,increase the content of P-Akt protein and P-Akt positive cell level,reduce the expression of VIP,reduce the content of NO and eNOS in colon tissues(P<0.05).Compared with Maren Soft Capsule group,low dosage group of Huayu Tongbian Decoction was similar to Maren Soft Capsule group(P>0.05),and the medium and high dosage groups of Huayu Tongbian Decoction were significantly better than Maren Soft Capsule group(P<0.05).Conclusion:Huayu Tongbian Decoction has therapeutic effect on rats with slow transit constipation by regulating PI3K/Akt/eNOS signaling pathway and VIP expression.