基于成分-药效对比分析鸡内金不同给药形式对功能性消化不良大鼠的疗效差异

Comparative analysis of efficacy of different forms of Galli Gigerii Endothelium Corneum on functional dyspepsia in rats based on composition-pharmacodynamics

基于现代分析技术和功能性消化不良(functional dyspepsia,FD)大鼠模型系统评价鸡内金不同入药形式化学成分和药效的差异性,为鸡内金消食功效物质基础提供依据。分别测定鸡内金散剂和汤剂蛋白质、酶、多糖、氨基酸及黄酮类成分,散剂和汤剂总蛋白分别为0.06%、0.65%;散剂胃蛋白酶和淀粉酶活力效价分别为27.03、44.05 U·mg^(-1);汤剂多糖为0.03%,散剂中未检出多糖;散剂和汤剂中L型氨基酸总量分别为279.81、8.27 mg·g^(-1);总黄酮质量分数为59.51μg·g^(-1),汤剂未能检测出酶和黄酮类成分。散剂可明显降低体外营养糊黏度,而汤剂与空白组对营养糊黏度降低无明显作用。采用碘乙酰胺灌胃结合不规则饮食法制备FD大鼠模型,结果显示,散剂和汤剂均可显著提高大鼠胃排空作用、小肠推进率、消化酶活力、血清胃泌素(gastrin,GAS)、胃动素(motilin,MTL)、饥饿素(ghrelin,GHRL)水平,显著降低血管活性肠肽(vasoactive intestinal peptide、VIP)、5-羟色胺[3-(2-ammonioethyl)-5-hydroxy-1H-indolium maleate,5-HT]、生长激素抑制素(somatostatin,SST)水平(P<0.05,P<0.01)。散剂和汤剂给药在同等剂量级别组之间比较,散剂组大鼠胃肠推进作用、血清GAS、GHRL、VIP和SST水平明显优于汤剂组,散剂组在胃肠推进作用、血清MTL、GAS、GHRL水平稍高于其2倍生药量的汤剂组,散剂组血清SST、5-HT、VIP水平稍低于其2倍生药量的汤剂组。综上,鸡内金汤剂与散剂对功能性消化不良均有治疗作用,但两者作用有较明显差异;同等剂量下,散剂消食药效明显优于汤剂,汤剂需增加剂量以补偿药效。推测鸡内金消食药效具有二元性,散剂的消食活性成分可能包括酶和L型氨基酸,汤剂主要依靠L型氨基酸发挥药效,该研究为探究鸡内金消食活性物质、提高临床用药效果提供了新证据。

A systematic evaluation of the differences in the chemical composition and efficacy of the different forms of Galli Gigerii Endothelium Corneum(GGEC) was conducted based on modern analytical techniques and a functional dyspepsia(FD) rat model,which clarifies the material basis of the digestive efficacy of GGEC.Proteins,enzymes,polysaccharides,amino acids,and flavonoids in GGEC powder and decoction were determined respectively.The total protein of the powder and decoction was 0.06% and 0.65%,respectively,and the pepsin and amylase potency of the powder was 27.03 and 44.05 U·mg~(-1) respectively.The polysaccharide of the decoction was 0.03%,and there was no polysaccharide detected in the powder.The total L-type amino acids in the powder and decoction were 279.81 and 8.27 mg·g~(-1) respectively,and the total flavonoid content was 59.51 μg·g~(-1).Enzymes and flavonoids were not detected in the decoction.The powder significantly reduced nutrient paste viscosity,while the decoction and control group showed no significant reduction in nutrient paste viscosity.FD rat models were prepared by iodoacetamide gavage and irregular diet.The results showed that both powder and decoction significantly increased the gastric emptying effect,small intestinal propulsion rate,digestive enzymes activity,gastrin(GAS),motilin(MTL),ghrelin(GHRL) and reduced vasoactive intestinal peptide(VIP),3-(2-ammo-nioethyl)-5-hydroxy-1H-indolium maleate(5-HT),and somatostatin(SST) content in rats(P<0.05,P<0.01).Comparison of GGEC decoction and powder administration between groups of the same dosage level showed that gastrointestinal propulsion and serum levels of GAS,GHRL,VIP,and SST in the powder group were significantly superior to those in the decoction and that the gastrointestinal propulsion,as well as serum levels of MTL,GAS,and GHRL were slightly higher than those of the decoction with two times its raw dose,and the serum levels of SST,5-HT,and VIP in the powder group were slightly lower than those of the decoction with two times its raw dose.In conclusion,both decoction and powder have therapeutic effects on FD,but there is a significant difference between the two effects.Under the same dosage,the digestive efficacy of the powder is significantly better than that of the decoction,and the decoction needs to increase the dosage to compensate for the efficacy.It is hypothesized that the digestive efficacy of the GGEC has a duality,and the digestive active ingredients of the powder may include enzymes and L-type amino acids,while the decoction mainly relies on L-type amino acids to exert its efficacy.This study provides new evidence to investigate the digestive active substances of the GGEC and to improve the effectiveness of the drug in the clinic.