多肽P Ⅲ术中与术后腹腔注射抑制胃癌腹膜转移的研究

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目的评价多肽PⅢ术中及术后早期腹腔内应用对胃癌腹膜转移的作用。方法48只裸鼠经完整组织块裸鼠胃壁原位种植,建立类似于临床的胃癌腹膜转移模型。每组16只,随机分为①对照组;②术中腹腔多肽灌洗+术后多肽治疗组(关腹前立即用60ml、43℃生理盐水溶解多肽PⅢ200μg冲洗腹腔2次);③术后多肽治疗组。术后1周开始治疗,对照组每只裸鼠与第8、10、12、14、16、18、20、22天腹腔各0·2ml生理盐水腹腔注射;②组和③组与对照组相同的时间分别给予多肽PⅢ2mg/kg腹腔注射,移植后第23天各取6只裸鼠脱颈处死,测定原位肿瘤重量,观察腹膜转移情况。其余裸鼠用于生存率试验。结果对照组、术中腹腔多肽灌洗+术后多肽治疗组和术后多肽治疗组的裸鼠原位肿瘤重量分别为(1·93±0·22)g、(1·81±0·36)g、(1·95±0·45)g,各组间比较,差异无统计学意义;对照组、术后多肽治疗组和术中腹腔多肽灌洗+术后多肽治疗组的裸鼠腹膜转移的瘤结节数分别为(126·3±9·6)个、(64·2±8·3)个、(9·2±1·3)个;其中大于2mm的裸鼠平均腹膜转移结节数分别为(51·2±3·6)个、(21·7±4·9)个、(1·6±0·2)个,与对照组比较,差异均有统计学意义(均P<0·01)。裸鼠生存试验显示术中腹腔多肽灌洗+术后多肽治疗组裸鼠生存时间明显长于对照组及术后多肽治疗组的裸鼠生存时间。结论多肽PⅢ术中及术后腹腔内用药可明显降低裸鼠胃癌腹膜转移的发生,显著延长了裸鼠的生存期,有望成为临床上治疗胃癌腹膜转移的药物。 Objective To evaluate the effect of intraperitoneal injection of polypeptide P Ⅲ intraperitoneally and postoperatively on peritoneal metastasis of gastric cancer. Methods Forty-eight nude mice were in situ implantation in the nude mouse stomach wall, and established a model of peritoneal metastasis resembling clinical. Sixteen rabbits in each group were randomly divided into ① control group; ② intraoperative intraperitoneal peptide lavage + postoperative peptide therapy group (60ml, 43 ℃ normal saline dissolved peptide P 200μg twice daily); ③ postoperative peptide therapy group. One week after the start of treatment, each nude mouse in the control group was intraperitoneally injected with 0.2 ml saline into the abdominal cavity on the 8th, 10th, 12th, 14th, 16th, 18th, 20th, Were given intraperitoneal injection of peptide P 2mg / kg intraperitoneally. After the transplantation, 6 nude mice were sacrificed on the 23rd day. The tumor weight in situ was measured and the peritoneal metastasis was observed. The remaining nude mice were used for survival tests. Results The in situ tumor weights of nude mice in control group, intraperitoneal peptide lavage + postoperative peptide therapy group and postoperative peptide therapy group were (1.93 ± 0.22) g, (1.81 ± 0.36 ) g and (1 · 95 ± 0 · 45) g, respectively. There was no significant difference between the two groups in the control group, postoperative peptide therapy group and intraperitoneal peptide lavage + postoperative peptide treatment group The number of metastatic nodules were (126.3 ± 9.6), (64.2 ± 8.3), (9.2 ± 1.3), respectively. The average peritoneal metastasis in nude mice larger than 2 mm (51.2 ± 3.6) nodules (21.7 ± 4.94) and (1.6 ± 0.2) nodules, respectively, which were significantly different from the control group (P < All P <0.01). Nude mice survival test showed intraperitoneal peptide lavage + postoperative peptide treatment group, the survival time of nude mice was significantly longer than the control group and postoperative peptide treatment group of nude mice survival time. Conclusion Intraperitoneal administration of polypeptide P Ⅲ intraperitoneally can significantly reduce peritoneal metastasis of gastric cancer in nude mice and prolong the survival of nude mice significantly. It is expected to become a drug for the clinical treatment of peritoneal metastasis of gastric cancer.
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