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目的 从细胞膜和细胞核水平对肾癌多药耐药机制进行探讨。方法 应用免疫组化方法对肾癌 M D R 的主要耐药指标 P 糖蛋白( Pgp) 、 D N A 拓扑异构酶Ⅱ( Topo Ⅱ) 进行检测。结果 88 .9 %的正常组织及65 .7 % 癌组织有 Pgp 表达,阳性染色位于正常近曲小管上皮或癌细胞膜和部分胞浆,表达强度与分级、分型无关,高期癌表达较低期癌强。21 .4 % 的癌组织 Topo Ⅱ表达阳性( Topo Ⅱ值≥100)阳性染色均位于胞核。表达1 种耐药指标者( Pgp 阳性或 Topo Ⅱ< 100) 占42 .9 % ,2 种耐药指标者占52 .9 % ,4 .2 % (3/70) 无耐性指标表达,两者之间存在负相关关系。结论 各型肾癌 Pgp 高表达,发挥药物排出泵的作用而产生 M D R。肾癌 Topo Ⅱ表达值显著降低,使大多数化疗药物丧失了作用靶点而产生 M D R。选择 Pgp 低表达同时 Topo Ⅱ高表达的患者并且针对不同 M D R 机制采用不同的化疗药物进行化疗将有助于提高化疗有效率。
Objective To investigate the mechanism of multidrug resistance of renal cell carcinoma (NPC) from the level of cell membrane and nucleus. Methods Immunohistochemical method was used to detect the main resistance indexes of renal cancer M D R, such as Pgp and Topo Ⅱ. Results 88. 9% of normal tissues and 65. 7% of the cancerous tissues had P-gp expression. The positive staining was located in the normal proximal tubule epithelium or the cancer cell membrane and some cytoplasm. The expression intensity had no correlation with the grade and the type of the tumor. 21. In 4% of the cancerous tissues, Topo Ⅱ expression was positive (Topo Ⅱ≥100) staining was located in the nucleus. Those who expressed a resistance index (P gp positive or Topo Ⅱ <100) accounted for 42%. 9%, two kinds of resistance index accounted for 52%. 9%, 4. 2% (3/70) intolerance indicators, there is a negative correlation between the two. Conclusion Various types of renal cell carcinoma P gp high expression, exert the role of drug discharge pump to produce MDR. Renal cancer Topo Ⅱ expression was significantly lower, so that most of the chemotherapy drugs lost the role of target and produce MDR. Choosing a patient with a low expression of P-gp and a high expression of Topo II and chemotherapy with different chemotherapeutic agents for different mechanisms of MDR will help improve the efficiency of chemotherapy.