慢性萎缩性胃炎是消化系统常见难治性疾病，属于胃癌前病变，缺乏有效治疗药物。前期研究表明针对慢性萎缩性胃炎脾阳虚证，ghrelin分泌紊乱为该病证关键病机，附子理中丸治疗该病证疗效满意，但药理机制有待深入研究。本课题提出“附子理中丸通过维护ghrelin稳态，治疗慢性萎缩性胃炎脾阳虚证”的工作假说。采用序贯干预法建立慢性萎缩性胃炎脾阳虚证大鼠模型，灌胃不同剂量附子理中丸治疗不同时间后，通过观察证候评分、胃肠功能、胃黏膜形态学改变，血浆ghrelin水平，确定经方的量效与时效；通过观察ghrelin分泌-大脑生长素受体水平-炎症介质变化，探索附子理中丸的药理机制。本课题为附子理中丸治疗慢性萎缩性胃炎脾阳虚证提供了科学依据。

Chronic atrophic gastritis is a common digestive disease, lacking effective drugs. In the previous studies, it was found that ghrelin is involved in the pathogenesis of this disease. Fuzi lizhong pill is a classic formula in traditional Chinese medicine with satisfactory effects in clinic, but the pharmacological mechanism is unknown. This study proposed the hypothesis that “Fuzi lizhong pill effects on chronic atrophic gastritis with Spleen-Yang deficiency via regulating ghrelin axis”. The sequential intervention methods were used to establish the chronic atrophic gastritis with spleen yang deficiency rat model. After treated with Fuzi lizhong pill, the symptom scale, gastrointestinal dynamics, and histological methods were used to detecte the Spleen-Yang deficiency syndrome, gastrointestinal functions, and pathological changes of gastric mucosa, which was to evaluated the pharmacodynamics of formula. Then the radioimmunoassay, enzyme-linked immunoassay, and molecular biotechnology were used to test the changes of gastrointestinal hormones-ghrelin axis- growth hormone receptor levels in brain -inflammatory mediators, and relations between each other, which was to determine the pharmacological targets and mechanisms of this formula. This study could supply scientific basis for the treatment of Fuzi lizhong pill for chronic atrophic gastritis with Spleen-Yang deficiency.

慢性萎缩性胃炎是消化系统常见癌前病变，缺乏有效治疗药物。前期发现ghrelin参与其脾阳虚证候发病，附子理中丸调节ghrelin分泌，但防治该病的药理机制未明。本课题(1)采用序贯干预法建立慢性萎缩性胃炎脾阳虚证大鼠模型，同时以附子理中丸验证；(2)确定方剂防治该病的量效关系；(3)采用酶联免疫、分子生物学等技术，检测血浆炎症介质、ghrelin在血浆和胃黏膜的变化、脑组织ghrelin受体分布，探索方剂的药理机制。结果显示(1)模型大鼠胃黏膜出现萎缩与化生基本病变，胃黏膜体积构成比显著下降，其阳虚与脾虚症状群与临床证候吻合，方剂治疗后病变减轻；(2)方剂防治该病的半数有效剂量为2857.00ng/kg，95%的置信区间为119.30- 68430.00ng/kg；(3)方剂可抑制IL-1β和TNF-α水平；升高血浆ghrelin水平，降低胃黏膜中ghrelin基因表达，增加其蛋白含量，降低其原位细胞表达水平；增加ghrelin受体表达。以上结果显示附子理中丸通过促进ghrelin释放，调节ghrelin稳态防治该癌前病变。本课题为附子理中丸防治胃癌前病变治未病提供了基础。