慢性浅表性胃炎脾虚证患者与健康人物质能量代谢基因差异表达研究

Research on Differentially Expressed Genes Related to Substance and Energy Metabolism between Healthy Volunteers and Splenasthenic Syndrome Patients with Chronic Superficial Gastritis

目的分析慢性浅表性胃炎脾虚证患者体内脂类、蛋白质、糖类和核酸代谢情况,从物质能量代谢的角度探讨脾虚证的病理发生机制。方法选择4例2004年6月—2005年3月就诊于广州中医药大学一附院和广东省中医院的慢性浅表性胃炎脾虚证患者,选择广州中医药大学健康人4名,钳取患者及健康人胃黏膜进行DNA芯片实验,利用BRB ArrayTools和IPA软件对DNA芯片双通道数据进行数据挖掘和生物信息学分析。结果获得15个与物质能量代谢相关差异基因,占总差异表达基因(20个)的75%,其中上调基因1个,下调基因14个,11个基因为酶基因。其中脂类代谢相关差异基因有ACAA2和CYP20A1,表现为脂肪酸分解和胆固醇转化降低;蛋白质代谢相关差异基因有ALDH9A1、ASL、ASS1、PCYOX1L、RPS28、UBE2D2、UBXN1、B3GNT1、GCNT1和PPP1R3C,表现为影响自主神经、尿素循环等生物学过程的氨基酸代谢降低,蛋白质合成降低,错误折叠蛋白泛素化降解增加,翻译后糖基化和磷酸化修饰降低;糖类代谢相关差异基因有PPP1R3C、B3GNT1和GCNT1,表现为糖原和聚糖合成降低;核酸代谢相关差异基因有RMI1、SMARCD3和PARP1,表现为DNA复制和转录降低,DNA损伤修复增加。结论慢性浅表性胃炎脾虚证患者体内脂类、蛋白质、糖类和核酸代谢水平明显降低,并且主要表现为酶基因表达下调,推测此可能是导致脾虚证营养代谢障碍的重要机制之一。

Objective To analyze the metabolic states of the lipids， protein， carbohydrate， and nucleic acid for chronic superficial gastritis patients of splenasthenic syndrome （SS）， and to explore the pathogenesis mechanism of SS based on substance and energy metabolisms. Methods During June 2004 to March 2005， recruited were four chronic superficial gastritis patients of SS who visited at the First Hospital of Guangzhou University of Chinese Medicine and Guangdong Provincial Hospital of Traditional Chinese Medicine. Four healthy volunteers were recruited from Guangzhou University of Chinese Medicine. Their gastric mucosa was extracted to perform experiments of DNA microarray. The dual channel DNA microarray data were mined and bioinformatically analyzed by BRB ArrayTools and IPA software. Results Fifteen genes were involved in substance and energy metabolisms in 20 differentially expressed genes， accounting for 75%. Among these genes， one gene was up regulated， 14 genes down regulated， and 11 genes were enzyme gene. Differentially expressed genes related to lipid metabolism included ACAA2 and CYP20A1， manifested as fatty acid catabolism and cholesterol transformation. Genes related to protein metabolism included ALDH9A1， ASL， ASS1， PCYOX1L， RPS28， UBE2D2， UBXN1， B3GNT1， GCNT1， and PPP1R3C， manifested as decreased amino acid metabolism that may affect the biologic processes such as autonomic nerve， urea cycle， etc.， reduced protein synthesis， increased ubiquitination of fault fold proteins， and decreased post translated modification of glycosylation and dephosphorylation. Genes related to carbohydrate metabolism included PPP1R3C， B3GNT1， and GCNT1， manifested as decreased glucogen and glycan syntheses. Genes related to nucleic acid metabolism included RMI1， SMARCD3， and PARP1， manifested as degraded DNA duplication and transcription， and increased DNA damage repair. Conclusions The metabolisms of the lipids， protein， carbohydrate， and nucleic acid in chronic superficial gastritis patients of SS obviously decreased， manifested mainly as down regulated enzyme gene expression. We inferred that these might be one of the vital pathogenesis mechanisms for nutrition dysmetabolism of SS.