胃癌患者的黏膜线粒体功能与抗氧化防御

Mucosal mitochondrial function and antioxidant defences in patients with gastric carcinoma.

作者信息

Eapen C E, Madesh M, Balasubramanian K A, Pulimood A, Mathan M, Ramakrishna B S

机构信息

Dept. of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore, India.

出版信息

Scand J Gastroenterol. 1998 Sep;33(9):975-81. doi: 10.1080/003655298750027010.

DOI:10.1080/003655298750027010

PMID:9759955

Abstract

BACKGROUND

Cancer cells have alterations in energy metabolism due to defective mitochondrial function. This may be due to generation of excessive free radicals and/or defective antioxidant enzyme systems. The aim of the present study was to assess mitochondrial function and antioxidant defences in the gastric mucosa of patients with gastric carcinoma (CA).

METHODS

Gastric mucosal mitochondrial function was assessed by means of the reduction of tetrazolium dye (MTT), and levels of antioxidants such as glutathione S-transferase (GST), catalase, superoxide dismutase (SOD), and thiols were measured in biopsy specimens taken from the tumour mucosa (TM) and tumour-free (TF) mucosa, 2 cm away from the tumour, in 49 patients with gastric CA and compared with that in 54 controls. In a further 10 patients with gastric CA, these studies were done on TM and TF mucosa 2 cm and > or = 5 cm away from the tumour. In 10 patients and 5 controls, specimens were obtained for electron microscopy as well. Helicobacter pylori infection was diagnosed by means of histology.

RESULTS

MTT reduction and GST and SOD activities were significantly decreased in TM and TF mucosa in patients with CA compared with controls (P < 0.01). The levels of thiols and catalase activity were significantly increased in CA as compared with controls (P < 0.01). H. pylori positivity did not influence most of these variables but did give significant decrease in MTT reduction in CA (TF) mucosa (P=0.01) and significant increase in thiol levels in CA (TM) mucosa (P=0.04). Electron microscopy showed mitochondrial alterations in tumour cells in all patients and in adjacent mucosa of 10%-50% of the cells.

CONCLUSIONS

In gastric CA the cancer mucosal cells and the non-involved cells adjacent to the tumour have defective mitochondrial function, which may be due to altered antioxidant defences and possibly altered free radical formation. 2) Ultrastructural mitochondrial abnormalities are shown to parallel these biochemical abnormalities.

摘要

背景

由于线粒体功能缺陷，癌细胞的能量代谢发生改变。这可能是由于过量自由基的产生和/或抗氧化酶系统缺陷所致。本研究的目的是评估胃癌（CA）患者胃黏膜中的线粒体功能和抗氧化防御能力。

方法

通过四唑盐染料（MTT）还原法评估胃黏膜线粒体功能，并在49例胃癌患者的肿瘤黏膜（TM）和距肿瘤2 cm的无肿瘤（TF）黏膜活检标本中测量抗氧化剂水平，如谷胱甘肽S-转移酶（GST）、过氧化氢酶、超氧化物歧化酶（SOD）和硫醇，并与54例对照进行比较。在另外10例胃癌患者中，对距肿瘤2 cm和≥5 cm的TM和TF黏膜进行了这些研究。在10例患者和5例对照中，还获取了用于电子显微镜检查的标本。通过组织学诊断幽门螺杆菌感染。

结果

与对照组相比，CA患者的TM和TF黏膜中MTT还原以及GST和SOD活性显著降低（P < 0.01）。与对照组相比，CA患者的硫醇水平和过氧化氢酶活性显著升高（P < 0.01）。幽门螺杆菌阳性对这些变量中的大多数没有影响，但确实使CA（TF）黏膜中的MTT还原显著降低（P = 0.01），并使CA（TM）黏膜中的硫醇水平显著升高（P = 0.04）；电子显微镜检查显示，所有患者的肿瘤细胞以及10%-50%细胞的相邻黏膜中线粒体均有改变。