香砂六君子汤对脾胃虚弱型萎缩性胃炎大鼠胃排空功能及胃蛋白酶活性和缺氧诱导因子—1α表达的影响

段云燕+成映霞+王强+李兰珍+王庆胜+郑世铎+鲁鹏程+雷作汉+刘雪松+刘臻华

摘要：目的 观察香砂六君子汤对脾胃虚弱型萎缩性胃炎（CAG）大鼠胃排空功能、胃蛋白酶活性、胃黏膜组织缺氧诱导因子-1α（HIF-1α）基因和蛋白表达的影响，探讨该复方防治CAG的作用机制。方法 受试大鼠按随机数字表法分为空白组和造模组，采用综合法复制脾胃虚弱型CAG动物模型，成模后将模型大鼠分为模型组、阳性对照组和香砂六君子汤高、中、低剂量组。空白组和模型组大鼠每日给予10 mL/kg蒸馏水灌胃，香砂六君子汤大、中、小剂量组每日分别给予24、12、6 g/kg香砂六君子汤药液灌胃，阳性对照组每日给予0.30 g/kg维霉素药剂灌胃，连续给药120 d，检测各组大鼠胃排空功能、胃蛋白酶活性，分别采用实时荧光定量PCR和免疫组化法检测胃黏膜组织HIF-1α基因及蛋白表达。结果 与空白组比较，模型组大鼠胃排空功能、胃蛋白酶活性显著降低（P<0.01），HIF-1α基因和蛋白表达水平显著升高（P<0.01）；与模型组比较，香砂六君子汤各组大鼠胃排空功能、胃蛋白酶活性升高，HIF-1α基因和蛋白表达水平降低，且以香砂六君子汤高剂量组作用显著（P<0.05）。结论 香砂六君子汤具有改善脾胃虚弱型CAG大鼠胃排空功能、促进胃蛋白酶活性、下调缺氧环境中HIF-1α基因和蛋白表达的作用。

关键词：胃排空功能；胃蛋白酶；缺氧诱导因子-1α；萎缩性胃炎；香砂六君子汤；大鼠

DOI：10.3969/j.issn.1005-5304.2016.01.011

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2016）01-0047-05

Effects of Xiangsha Liujunzi Decoction on Gastric Emptying Function， Pepsin Activity and Expression of HIF-1α in Chronic Atrophic Gastritis of Rats with Deficiency Spleen and Stomach DUAN Yun-yan1，2， CHENG Ying-xia1，2， WANG Qiang1， LI Lan-zhen2， WANG Qing-sheng1， ZHENG Shi-duo2， LU Peng-cheng2， LEI Zuo-han3， LIU Xue-song1， LIU Zhen-hua1 （1. Gansu University of Chinese Medicine， Lanzhou 730020， China； 2. Key Laboratory of Traditional Chinese Herbs and Prescription Innovation and Transformation of Gansu Province， Lanzhou 730020， China； 3. Gansu Chinese Medicine Hospital， Lanzhou 730020， China）

Abstract： Objective To study effects of Xiangsha Liujunzi Decoction （XSLJZ） on gastric emptying function， pepsin activity and expression of HIF-1α gene and protein of gastric mucosa in chronic atrophic gastritis （CAG） of rats with deficiency of spleen and stomach. Methods Rats were randomly divided into normal group and model group. The models of CAG rats with deficiency of spleen and stomach type were induced by synthetic methods. After the modeling， models rats were divided into model group， positive control group and XSLJZ high-， medium-， and low-dose groups. Normal group and model group were given 10 mL/kg distilled water every day for gavage； XSLJZ high-， medium-， and low-dose groups were given 24， 12， and 6 g/kg XSLJZ Decoction for gavage； positive control

group was given 0.30 g/kg Vatacoenayme for gavage， for successive 120 d. Gastric emptying function and pepsin activity were detected， and HIF-1α gene and protein expression in gastric mucosa were detected by RT-qPCR and IHC. Results Compared with the normal group， the gastric emptying function and pepsin activity in the model group were much lower （P<0.01）； expressions of HIF-1α gene and protein in gastric tissues was much higher （P<0.01）. Compared with model group， XSLJZ could increase the gastric emptying function and pepsin activity significantly （P<0.05）， and decrease expressions of HIF-1α gene and protein （P<0.05）. Conclusion XSLJZ has functions of improving the gastric emptying function， promoting pepsin activity， and reducing expressions of HIF-1α gene and protein.

Key words： gastric emptying function； pepsin； HIF-1α； atrophic gastritis； Xiangsha Liujunzi Decoction； rats

慢性萎缩性胃炎（chronic atrophic gastritis，CAG）作为消化系统常见病，尤其在CAG伴有肠上皮化生和异常增生时，易引起继发性胃癌，严重威胁生命质量。就其临床病症特点而言，中医认为CAG多以脾胃虚弱、气机或气血失调为主要病机，故治疗多以健脾益气、理气和胃为大法。香砂六君子汤出自《古今名医方论》。临床应用显示，香砂六君子汤及其加减方治疗CAG疗效显著[1-2]。本研究通过观察香砂六君子汤对脾胃虚弱型CAG大鼠胃排空功能、胃蛋白酶活性及胃窦黏膜缺氧诱导因子-1α（HIF-1α）基因和蛋白表达的影响，探讨该复方防治CAG的作用机制。……