新疆肝癌脾虚湿盛证的代谢组学研究

Liver cancer is one of the Xinjiang high tumor, its incidence, the mortality rate increases year by year. Because of the Xinjiang region, restaurants and ethnic characteristics, common licence and clinical manifestations in patients with hepatocellular carcinoma in Xinjiang and the nature and characteristics of pathogenic dampness disease similar to used clinically treated with jianpi dampness and achieved good results. This project application metabolism group learn technology and method, from medical spleen virtual wet Sheng led to liver cancer occurred of disease machine features start, select Xinjiang liver cancer patients for research object, extraction Xinjiang liver cancer spleen virtual wet Sheng card group and the non-spleen virtual wet Sheng card group, and non-tumor group spleen virtual wet Sheng card health spleen of wet law treatment before and after plasma, and urine liquid, according to NMR spectrum technology judgment metabolism property ingredients and the relative content, exploring Xinjiang liver cancer patients of special heterosexual metabolism logo property, while exploration liver cancer spleen virtual wet Sheng card of objective material based One hand reveal jianpi dampness Chinese medicine in treatment of molecular biological effects, liver and spleen damp Shing permit early diagnosis, prognosis, drug treatment and other aspects provide a certain basis.

肝癌是新疆特高发肿瘤之一，其发病率，死亡率逐年增高。由于新疆的地域、饮食及民族特点，使新疆肝癌患者常见病证及临床表现与湿邪为病的性质和特点相似，临床上运用健脾化湿法治疗取得了较好的疗效。本项目应用代谢组学技术和方法，从中医学脾虚湿盛导致肝癌发生的病机特点入手，选取新疆肝癌患者为研究对象，提取新疆肝癌脾虚湿盛证组及非脾虚湿盛证组、非肿瘤组脾虚湿盛证健脾化湿法治疗前后血浆、尿液,根据核磁共振波谱技术判断代谢物成分及相对含量，探寻新疆肝癌患者的特异性代谢标志物，一方面探索肝癌脾虚湿盛证的客观物质基础；另一方面揭示中医健脾化湿法治疗的分子生物学效应，为肝癌脾虚湿盛证的早期诊断、预后评估、药物干预治疗等方面提供一定依据。

本项目通过研究新疆肝癌脾虚湿盛证患者血浆、尿液代谢组学的变化，探讨新疆肝癌脾虚湿盛证患者体内代谢的变化及可能的特征性生物标志物。通过对130例肝癌脾虚湿盛证患者、190例肝癌非脾虚湿盛证患者和227名健康体检者进行血浆核磁共振氢谱检测，选取35例肝癌脾虚湿盛证患者、35例肝癌非脾虚湿盛证患者和40名健康人的尿液进行核磁共振检测。谱图经处理后对谱图分段积分结果进行分析，经OPLS-DA分析发现，肝癌脾虚湿盛证与非脾虚湿盛证代谢谱明显不同，肝癌脾虚湿盛证患者血浆中亮氨酸、异亮氨酸、缬氨酸、丙氨酸、谷氨酰胺、谷氨酸、组氨酸、甘氨酸、酪氨酸、苯丙氨酸等多种氨基酸含量较肝癌非脾虚湿盛证患者明显降低(P<0.05)，血浆中肌酸、肌酸酐等代谢物含量也明显降低(P<0.05)，而肝癌脾虚湿盛证患者血浆中乳酸、丙酮、β-葡萄糖、α-葡萄糖、不饱和脂类等代谢物含量却升高(P<0.05)。肝癌脾虚湿盛证患者尿中肌酐、马尿酸、氧化三甲胺（TMAO）、柠檬酸、丙氨酸、亮氨酸、谷氨酸含量较肝癌非脾虚湿盛证降低（P<0.05），而牛磺酸、琥珀酸的含量显著高于肝癌非脾虚湿盛证组,新疆肝癌脾虚湿盛证与非脾虚湿盛证患者血浆、尿液代谢物含量差异显著，肝癌脾虚湿盛证可能的代谢表型是亮氨酸、异亮氨酸、缬氨酸、丙氨酸、谷氨酰胺、谷氨酸、组氨酸、甘氨酸、酪氨酸、苯丙氨酸、肌酸、肌酸酐、乳酸、丙酮、β-葡萄糖、α-葡萄糖、不饱和脂类等，其中又以缬氨酸、甘氨酸、β-葡萄糖差异最大，可考虑作为代谢产物的标志物来监测。肝癌脾虚湿盛证患者的糖代谢、氨基酸代谢以及脂代谢的差异，能量代谢和蛋白质代谢的异常，说明其预后可能比肝癌非脾虚湿盛证患者差。肝癌脾虚湿盛证患者在健脾化湿法治疗后血浆中亮氨酸、异亮氨酸、缬氨酸、丙氨酸、谷氨酰胺、谷氨酸等多种氨基酸含量有所增高（P<0.05），说明健脾化湿法改善了肝癌脾虚湿盛证患者的代谢，特别是改善了氨基酸的代谢。由此推测肝癌不同证型的生物学基础不同。