卡铂复合液对大鼠腹腔内化疗后腹膜Ⅰ型和Ⅲ型胶原mRNA表达的影响

Effect of Carboplatin Mixture Liquid on the Expression of Type I and type Ⅲ Collagen mRNA Levels of the Peritoneum After Intraperitoneal Chemotherapy

为进一步探讨含有透明质酸钠和人体白蛋白的卡铂复合液对腹腔内化疗后腹腔粘连的抑制作用。方法:采用斑点杂交和原位杂交方法观察卡铂复合液对大鼠腹腔内化疗后腹膜组织Ⅰ型和Ⅲ型胶原mRNA水平影响。结果:卡铂复合液腹腔内化疗后第21天和第48天大鼠腹膜组织中α_1(Ⅰ)和α_1(Ⅲ)胶原mRNA水平明显低于卡铂液组(P<0.01),其腹腔内粘连发生率和粘连程度显著低于卡铂液组(P<0.001)。原位杂交结果显示,胶原mRNA银颗粒与化疗后腹膜间皮细胞下成纤维细胞的增生分布重合,卡铂液组大鼠腹腔内化疗后腹膜明显增厚,间皮细胞下成纤维细胞增生活跃,细胞内可见大量的银颗粒;而卡铂复合液组大鼠腹膜下成纤维细胞增生明显受到抑制,银颗粒数量明显减少。结论:本研究提示卡铂复合液具有明显减少成纤维细胞胶原合成和抑制腹腔粘连形成的作用,是一种较理想的腹腔内化疗药液,值得临床推广应用。

It has been suggested that intraabdominai adhesion formationand peritoneal fibrosis are the main causes of the inablility of drug-containing fluid to be adequately distributed throughout peritoneal cavity and increasing complications of intraperitoneal chemotherapy. Method: The present study was designed to investigate effect of the carboplatin mixture liquid, containing carboplatin(1mg/ml), sodium hyaluronate(75mg/ml) and albumin(100mg/ml) on type I and type Ⅲ collagen mRNA levels of the peritoneum after intraperitoneal chemotherapy. Results: The dot blot results showed that α1(I) andα1(Ⅲ) mRNA levels increased significantly on 21st and 48th days after intraperitoneal chemotherapy with carboplatin liquid in rats. The mRNA levels decreased more significantly in the rats treated with carboplatin mixture liquid than those treated with carboplatin liquid. With in situ hybridization, the studies showed that the silver grains of type I and typeⅢcollagen were scattered within the fibroblasts in the peritoneum. The amounts of mRNA silver grains decreased more significantly in the group treated with carboplatin mixture liquid that that treated with carboplatin liquid (P<0.01). Conclusion: Intraperitoneal chemo-therapy with carboplatin mixture liquid may inhibit(over expression of collagen gene in peritoneum, and inhibit intraabdominal adhesion formation. The liquid is more suitable for the intraperitoneal chemotherapy of malignant tumour.