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开胃进食汤超微配方颗粒对脾虚证胃肠激素调节作用的研究
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摘要
第一部分开胃进食汤超微配方颗粒治疗脾虚证的临床研究
     目的:评价开胃进食汤超微配方颗粒治疗脾虚证的临床疗效,观察其对胃肠激素的影响。
     方法:采用随机对照实验方法对90例辨证为脾虚证患者分为3组,分别予开胃进食汤超微配方颗粒等倍剂量、1/2剂量、健胃消食片治疗,以2周为一疗程,观察各组治疗前后临床症状变化及血浆GAS、SST、MTL水平。
     结果:1.开胃进食汤超微等倍组总有效率为86.67%,1/2剂量组为83.33%,两者临床疗效基本相当,显效率均较健胃消食片组为优(P<0.05)。2与治疗前比较,开胃进食汤超微等倍组、超微1/2组、健胃消食片组均能升高血浆GAS、MTL水平,降低SST水平,组间比较差异无统计学意义。
     结论:开胃进食汤超微配方颗粒能明显改善脾虚患者临床症状,1/2剂量组与等倍组疗效基本相当;开胃进食汤超微配方颗粒能明显改善脾虚患者胃肠激素水平,使之趋于正常。
     第二部分开胃进食汤超微配方颗粒对大鼠胃液分泌的影响
     目的:研究开胃进食汤超微配方颗粒对正常大鼠及利血平所致脾虚证大鼠胃液分泌的影响
     方法:采用完全随机对照设计方案,选用健胃消食片作阳性药物对照,观察开胃进食汤超微配方颗粒等倍剂量、1/2剂量、1/4剂量、传统汤剂对正常SD大鼠胃液分泌的影响,找出最佳有效剂量,在此基础上进一步观察开胃进食汤对利血平所致脾虚大鼠胃液分泌的影响。
     结果:1与正常对照组比较,健胃消食片组、开胃进食汤传统汤剂组和超微配方颗粒各剂量组均能增加正常大鼠的胃液分泌量,降低胃液PH值,使胃液中游离酸、总酸度及总酸排出量明显增加,能明显增加胃蛋白酶活性;在增加幅度方面,超微1/2组与超微等倍组作用基本相当,优于超微1/4组(P<0.05),亦较传统汤剂组、健胃消食片组为强,但无统计学意义。2.与脾虚模型组比较,健胃消食片组、开胃进食汤传统汤剂组和超微1/2组的胃液分泌量,游离酸、总酸度及总酸排出量均减少,胃蛋白酶活性降低,PH值升高;且超微1/2组较健胃消食片组、传统汤剂组减少明显,但亦无统计学意义。
     结论:开胃进食汤超微配方颗粒对大鼠胃液分泌具有双向作用。1.促进正常大鼠胃液和胃酸的分泌,增加胃蛋白酶活性,且促进作用随剂量的增加有所增强,以1/2剂量为最佳;2.抑制利血平所致脾虚大鼠胃液和胃酸的分泌,降低胃蛋白酶活性。
     第三部分开胃进食汤超微配方颗粒对脾虚证大鼠组织和血浆GAS、SST、MTL含量的影响
     目的:观察开胃进食汤微配方颗粒对正常大鼠及利血平所致脾虚证大鼠组织和血浆GAS、SST、MTL含量的影响。
     方法:取SD大鼠60只,随机分为正常对照组、正常超微组、脾虚对照组、脾虚超微组、传统汤剂组、健胃消食片组,用利血平造成脾虚模型,正常组用生理盐水造模,然后分别予生理盐水、开胃进食汤超微配方颗粒1/2剂量混悬液、健胃消食片溶液灌胃,2周后提取标本,用放射免疫法(RIA)检测各组相关组织、血浆GAS、SST、MTL水平。
     结果:1.正常超微组组织、血浆GAS、MTL水平显著高于正常对照组(P<0.01),SST水平低于对照组(P<0.05);2.脾虚超微组、传统组、健胃消食片组组织、血浆GAS水平均显著低于脾虚模型组,SST、MTL水平则显著高于脾虚模型组;3.组间比较,脾虚超微组组织、血浆GAS水平低于传统汤剂组和健胃消食片组,SST、MTL水平高于传统汤剂组和健胃消食片组,与健胃消食片组比较P<0.05。
     结论:开胃进食汤超微配方颗粒对大鼠胃肠激素的调节呈现双向作用。
     1.刺激正常大鼠分泌GAS、MTL,抑制SST的分泌;2.能升高利血平所致脾虚大鼠组织、血浆SST、MTL水平,降低组织、血浆GAS水平。表明开胃进食汤能调节脾虚大鼠之胃肠激素紊乱,使之趋向正常。
     第四部分开胃进食汤超微配方颗粒对大鼠胃窦粘膜GAS、SSTR1mRNA表达的调节
     目的:研究开胃进食汤超微配方颗粒对正常大鼠及脾虚证大鼠胃窦粘膜GAS、SSTR1mRNA表达的影响,探讨其调节相关胃肠激素水平的分子机制。
     方法:在第三部分留取标本的基础上,运用RT-PCR方法测定各组胃窦粘膜GASmRNA、SSTR1mRNA的表达。
     结果:1.开胃进食汤超微配方颗粒可上调GASmRNA在正常大鼠胃粘膜的表达水平,而减弱其在脾虚大鼠胃粘膜的表达;2.开胃进食汤超微配方颗粒可减弱SSTR1mRNA在正常大鼠胃粘膜的表达水平,上调其在脾虚大鼠胃粘膜的表达。
     结论:开胃进食汤超微配方颗粒通过上调正常大鼠胃粘膜GASmRNA的表达、减弱SSTR1mRNA的表达,以及通过上调脾虚大鼠胃粘膜SSTR1mRNA的表达、减弱GAsmRNA的表达来调节胃肠激素的分泌,进而调节胃液、胃酸的分泌,在一定程度从分子水平上阐述了开胃进食汤通过调节胃肠激素治疗脾虚证的机制。
PartⅠClinic research on Spleen deficiency treated by Kaiwei Jinshitang ultramicro-drug piece
     Objective:To evaluate the clinical effect of Kaiwei Jinshitang(KWJST) ultramicro-drug piece(UMDP) on Spleen deficiency,and the gastrointestinal hormone changes.
     Method:90 patients with Spleen deficiency were divided randomly into three groups,treated with one dose and half dose of KWJST UMDP and Jianwei Xiaoshi Tablet(JWXST) respectively,two weeks for one period of treatment,the serum gastrin(GAS),somatostatin(SST) and motilin(MTL) were selected as evaluating items.
     Results:1.The total effect rate of one dose and half dose of KWJST UMDP were 86.67%and 83.33%respectively and the clinic efficacy were equal.The effective rate of KWJST UMDP was higher than that of JWXST(P<0.05).2.One dose and half dose of KWJST UMDP and JWXST could raise serum GAS and MTL,while reduce SST,and there were no significant difference among them.
     Conclusion:KWJST UMDP could improve the symptom of Spleen deficiency, the half dose group equals to one dose group.KWJS UMDP could prompt GAS and MTL,as well inhibit SST secretion.
     PartⅡThe effect of KWJST UMDP on rats' gastric juice secretion
     Objective:To study the effect of KWJST UMDP on the gastric juice secretion in normal rats and Spleen deficiency rats induced by reserpine.
     Method:In order to find out the best dose,random comparing design applied, and JWXST selected as positive contrast drug,one dose,half dose and one fourth dose of KWJST UMDP,and traditional decoction of KWJST respectively were used to observe the effect of the above materials on the normal SD rats' gastric juice secretion.And the effect of KWJST UMDP on the gastric juice secretion in Spleen deficiency rats induced by reserpine was also evaluated.
     Results:1.Comparing to normal group,JWXST and traditional decoction and different doses UMDP of KWJST could increase rats gastric juice secretion, decreasing gastric juice PH value,increasing free acid and total acidity and output of total acid,as well pepsin activity.As for the increasing amplitude,half dose of KWJST UMDP equaled to one dose,and was higher than one fourth dose(P<0.05). While there were no significant difference among traditional decoction and half dose of KWJST UMDP and JWXST.2.Comparing to Spleen deficiency group, the gastric juice,free acid,total acidity and output of acid were lower in JWXST, traditional decoction and half dose of KWJST,as well as pepsin activity,while the higher PH value in later three groups.And for the above items,there were no significant difference among the later three groups.
     Conclusion:KWJST UMDP has double effects on rats' gastric juice secretion.1. It could promote normal rats' gastric juice and acid secretion,and increase pepsin activity.With the higher dose,the higher effects appear,and half of dose has best effects.2.It could also inhibit gastric juice and acid secretion and pepsin activity in Spleen deficiency rats induced by reserpine.
     PartⅢThe effect of KWJST UMDP on Spleen deficiency rats' GAS,SST and MTL content in tissue and serum respectively
     Objective:To explore the effect of KWJST UMDP on GAS,SST and MTL content in tissue and serum of normal rats and Spleen deficiency rats induced by reserpine.
     Method:60 SD rats were randomly divided into normal contrast group,normal group with KWJST UMDP,Spleen deficiency group,Spleen deficiency treated with KWJST UMDP,traditional decoction group,JWXST group.Spleen deficiency group were induced by reserpine,and normal contrast group with normal saline.Then normal saline,half dose of KWJST UMDP and JWXST intragastric administration for two weeks,the tissue and serum GAS,SST and MTL were assayed respectively by radioimmunoassay(RIA).
     Results:1.The tissue and serum GAS and MTL in the normal group with KWJST UMDP were higher than those in normal contrast group significantly (P<0.01),while the SST was lower in the normal group with KWJST UMDP(P<0.05).2.Both of the tissue and serum GAS in Spleen deficiency treated with KWJST UMDP,traditional decoction of KWJST and JWXST,were lower than those in Spleen deficiency group,while SST and MTL were higher than those in Spleen deficiency group.3.Among the groups,the tissue and serum GAS were lower in Spleen deficiency treated with KWJST UMDP than those in traditional decoction of KWJST and JWXST,while the SST and MTL were higher.
     Conclusion:KWJST UMDP has double regulating function for rats' gastrointestinal hormone.1 It could stimulate normal rats with more GAS and MTL secretion,inhibiting SST secretion.2 It could raise the tissue and serum SST and MTL and reduce GAS level in the Spleen deficiency rats induced by reserpine. It shows that KWJST UMDP could regulate the inordinate gastrointestinal hormone for the normal level.
     PartⅣThe regulation of KWJST UMDP on normal rats and Spleen deficiency rats' GAS mRNA and SSTR mRNA expression in sinuses ventriculi mucosa
     Objective:To observe the effect of KWJST UMDP on normal and Spleen deficiency rats' GAS and SSTR mRNA expression in sinuses ventriculi mucosa, and explore the molecular mechanism of regulating gastrointestinal hormone.
     Method:RT-PCR was used for GAS mRNA and SSTR mRNA expression in rats' sinuses ventriculi mucosa.
     Results:1.KWJST UMDP could up-regulate GAS mRNA expression in sinuses ventriculi mucosa of the normal rats,while weakening its expression in the Spleen deficiency rats.2.KWJST UMDP could weaken SSTR mRNA expression in sinuses ventriculi mucosa of the normal rats,while up-regulating its expression in the Spleen deficiency rats
     Conclusion:KWJST UMDP could regulate gastrointestinal hormone by way of up-regulating GAS mRNA and down-regulating SSTR mRNA expression in normal rat,up-regulating SSTR mRNA and down-regulating SSTR mRNA expression in Spleen deficiency rat.And it is the base for regulating gastric juice and acid secretion,which is the molecular mechanism of KWJST UMDP treating Spleen deficiency in a way.
引文
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