【作者】 曹建雄；

【导师】 蔡光先；

【作者基本信息】 湖南中医药大学 ， 中医内科学， 2007， 博士

【摘要】 目的观察验证开胃进食汤超微颗粒治疗小儿厌食症的临床疗效,探讨其对幼龄厌食症大鼠胃窦粘膜超微结构的修复作用和脑肠肽——食欲中枢的调节作用,从而揭示其抗厌食的可能机理。方法1、将小儿厌食症患儿108例随机分成三组,分别口服开胃进食汤超微颗粒、开胃进食汤煎液和健胃消食片,经治一疗程后观察其临床疗效。2、模拟小儿厌食症病因,通过喂养特制饲料和灌胃大黄煎液建立脾虚失健型幼龄厌食症大鼠模型。3、幼龄厌食症大鼠模型建成后,应用开胃进食汤超微颗粒治疗,利用透射电镜观察其胃窦粘膜超微结构,图像分析仪分析上皮细胞和壁细胞内线粒体及主细胞酶原颗粒的个数、面积、周长、长径、短径及圆度值的变化。放免法和放射配基结合分析法检测中枢、外周β-内啡肽(β-EP)、八肽胆囊收缩素(CCK-8)及其受体变化情况。结果1、经一个疗程观察,三组患儿均取得较好疗效,总有效率在86%以上,组间对比无统计学意义,但开胃进食汤超微颗粒在显效病例数、降低症候积分、增加进食量及净增体重方面具有明显优势,与阳性组比较差异有统计学意义(P＜0.05或P＜0.01)。.2、幼龄厌食症大鼠模型进食量比空白组低40—50%,体重低10%—15%以上,差异均有统计学意义(P＜0.01),并出现便溏,毛枯不泽,少动等表现。经开胃进食汤超微颗粒治疗一疗程后,食量基本恢复正常,体重明显增加,与空白组对比均无统计学意义(P＞0.05),且一般情况大为改善,大便正常,毛亮光泽,活动自如。3、与空白组比较,幼龄厌食症大鼠胃窦粘膜上皮细胞和壁细胞内线粒体及主细胞酶原颗粒的个数、面积、周长、长径、短径及圆度值等发生明显变化,差异有统计学意义(P＜0.05或P＜0.01);而开胃进食汤超微颗粒组胃窦粘膜细胞超微结构明显改善,与模型组、自然恢复组比较,差异有统计学意义(P＜0.05或P＜0.01),与空白组的差异无统计学意义。与空白组相比,幼龄厌食症大鼠下丘脑、血浆和胃窦β-内啡肽均明显降低,其差异有统计学意义(P＜0.05或P＜0.01),下丘脑、血浆中八肽胆囊收缩素浓度增高,其差异有统计学意义(P＜0.05或P＜0.01);而开胃进食汤超微颗粒组下丘脑、血浆、胃窦粘膜的β-内啡肽浓度显著增加,下丘脑、血浆中八肽胆囊收缩素明显下降,与模型组比较,差异有统计学意义(P＜0.05或P＜0.01),与空白组的差异无统计学意义。与空白组相比,幼龄厌食症大鼠下丘脑和胃窦粘膜β-内啡肽受体最大结合数明显下降,下丘脑和幽门括约肌八肽胆囊收缩素受体最大结合数明显上升,其差异均有统计学意义(P＜0.01);而开胃进食汤超微颗粒组下丘脑和血浆、胃窦粘膜β-内啡肽受体最大结合数则明显上升,下丘脑、幽门括约肌八肽胆囊收缩素受体最大结合数下降,与模型组、自然恢复组及阳性组比较,差异有统计学意义(P＜0.05或P＜0.01),与空白组相比其差异无统计学意义。结论1、开胃进食汤超微颗粒是治疗小儿厌食症的有效方药,临床应用简便、快捷、经济和安全。2、模拟小儿厌食症病因建立脾虚失健型幼龄厌食症大鼠模型,方法简便,状态稳定,该模型可用于小儿厌食症的发病机理和药效学研究。3、幼龄厌食症大鼠胃窦粘膜细胞超微结构异常与厌食症的发生有关,而开胃进食汤超微颗粒能有效修复其异常结构,这是其促进其消化改善厌食的重要途径。开胃进食汤超微颗粒能通过促进幼龄厌食症大鼠食欲中枢和外周血、胃窦β-内啡肽的合成与分泌,抑制八肽胆囊收缩素的合成与分泌;增加幼龄厌食症大鼠食欲中枢和胃窦粘膜β-内啡肽受体最大结合数,减少食欲中枢和幽门括约肌八肽胆囊收缩素受体最大结合数。一方面直接促进胃肠的消化,另一方面通过对食欲中枢的调节作用,从而恢复食欲中枢的正常功能,达到增加食欲的目的,这种中枢性调节在幼龄厌食症大鼠增加食欲的过程中,起主导作用。修复小儿厌食症大鼠胃窦粘膜,并调节脑肠肽及其受体对外周、尤其是对食欲中枢的作用,这可能是开胃进食汤超微颗粒抗厌食作用主要机理之一。更多还原

【Abstract】 ObjectiveTo observe the clinical effect for child anorexia,the renovation of ultramicrostructure of sinuses ventriculi mucosa and the adjustment of appetite center in juvenile rat model with anorexia by taken KAI WEI JIN SHI ultrafine particle.It was expected to reveal possibility mechanism of treating anorexia.Methods1.108 patients with child anorexia by feeded respectively with KAI WEI JIN SHI ultrafine particle,KAI WEI JIN SHI TANG and JIAN WEI XIAO SHI PIAN were divided into three groups in random.2.Juvenile rat models with PI XU SHI JIAN anorexia were established by feeded special forage and DA HUANG Tea,and simulating the cause of child anorexia.3.Ultrastructure of sinuses ventriculi mucosa of juvenile rat models with anorexia was observed by transmission electron microscope(TEM). Mitochondrial in epicyte and oxyntic cells and the changes of quantity,area, perimeter,major axis,minor axis,roundness number of chief cell zymogen grain were analysised with quantimet.β-endorphin(β-EP) in center and peripheral blood,sinuses ventriculi mucosa,Octa-cholecystokinin(CCK-8) and it’s receptor were examined with radioimmunoassay(RIA). Results1.It was shown that the total effective rate were over 86%within one cause of treatment and there was no statistical significance in the three groups. Symptomes and physical sign in the group feeded with KAI WEI JIN SHI ultrafine particle was improved predominantly.Food-intake and body weight were increased simultaneously.It showed a statistical significance by compared with matched group(P＜0.05 or P＜0.01).2.It was shown that food-intake of juvenile rat models with anorexia were 40～50%lower than normal control,and weight 10%～15%lower before feeded with KAI WEI JIN SHI ultrafine particle(P＜0.01).It was righten after treatment and shown no statistical significance by compared with matched group(P＞0.05).3.It was shown that Mitochondrial in epicyte and oxyntic cells of sinuses ventriculi mucosa of juvenile rat models with anorexia,and the quantity,area, perimeter,major axis,minor axis,roundness number of chief cell zymogen grain changed obviously.There was a statistical significance by comparing with normal control(P＜0.05 or P＜0.01),and no significance in ultrastructure between the group feeded with KAI WEI JIN SHI ultrafine particle and normal control.β-EP in hypothalamus,plasma and sinuses ventriculi of juvenile rat models with anorexia were lower than normal control(P＜0.05 or P＜0.01), CCK-8 were higher(P＜0.05 or P＜0.01).Statistic above include it’s acceptor were changed into normal after being feeded with KAI WEI JIN SHI ultrafine particle(P＜0.01).Conclusion1.It was suggested that KAI WEI JIN SHI ultrafine particle was effective for child anorexia,which taken conveniently,quickly and economically.2.It was suggested that juvenile rat models with PI XU SHI JIAN anorexia established by feeded with special forage and DA HUANG tea to simulating the cause of child anorexia was stable and credible,which was useful for study on pathogenesis and pharmacodynamics of child anorexia.3.It was suggested that the occurrence of anorexia concerned with the abnormal ultrastructure of sinuses ventriculi mucosa of juvenile rat models with anorexia.KAI WEI JIN SHI ultrafine particle might intervent the abnormal ultrastructure effectively,promote synthesize and excretion ofβ-EP in hypothalamus,plasma and sinuses ventriculi of juvenile rat models with anorexia,increse acceptor,represse CCK-8 and it’s acceptor.It was conclused that KAI WEI JIN SHI ultrafine particle be ability to renovate sinuses ventriculi mucosa and adjust appetite center.It might be mechanism treating anorexia.更多还原