盐酸拓扑替康腹腔注射对大鼠腹腔器官及外周血白细胞的影响

Influence of topotecan hydrochloride on the organs in peritoneal cavity and leukocyte count of peripheral blood in rats.

目的 :探索拓扑替康腹腔化疗的安全性和可行性。方法 :以健康SD雌性大鼠为研究对象 ,观察拓扑替康腹腔化疗对大鼠腹腔内器官和外周血白细胞的影响。结果 :在剂量与静脉化疗总量相同和加大一倍时 ,拓扑替康腹腔化疗除引起与对照组相同的子宫炎症反应外 ,大网膜产生炎症反应 ;对卵巢和胰腺等则均无明显影响 ;当应用 4倍剂量时 ,造成胰腺实质间质部炎症反应。对外周血白细胞计数的影响与剂量有关 ,虽然各剂量腹腔化疗后第 3天 ,外周血白细胞计数都有下降 ,但仅在相当于静脉化疗剂量 2倍时 ,下降有统计学意义 ,剂量加大至 4倍时 ,虽然无统计学意义 ,但此实验组的白细胞计数在化疗后 5天无明显回升 ,直至化疗后 8天才恢复。其他实验组白细胞计数在化疗后 5天已回升至化疗前水平。结论 :拓扑替康腹腔化疗对大鼠外周血白细胞计数无严重影响 ,在适当剂量下对腹腔各正常器官也无明显刺激 ,对其一般情况等无明显作用。所以 ,在适当剂量下拓扑替康腹腔化疗是安全的 ,它为治疗卵巢肿瘤 ,特别是晚期、复发及耐药的卵巢肿瘤提供了新的途径。

Objective:To explore the practical and safe intra peritoneal chemotherapy with topotecan.Methods:The changes of peritoneal organs and WBC count of peripheral blood of SD rats after intra peritoneal chemotherapy with topotecan were observed.Results: When the dose of topotecan of intraperitoneal chemotherapy was equal to or two times as the total dose of intravenous chemotherapy,the inflammation was observed in uterus which also was observed in control group.Certain inflammation was observed in omentum which occasionally seen in control group,but nothing changed in ovary and pancreas.When the dose of topotecan increased to 4 times as that of intravenous chemotherapy,inflammation was observed in the parenchyma of pancreas.Furthermore,the positive relationship existed in the decreasing of WBC count and drug's dose.The WBC count decreased at the third day after intraperitoneal chemotherapy in all of study groups.The difference between WBC count at third day and the day before chemotherapy in the group whose dose was 2 times as that of intravenous chemotherapy was significant.At the fifth day after chemotherapy,the WBC count in the groups whose dose equaled to or was two times as the total dose of intravenous chemotherapy had increased to the level of WBC before chemotherapy.On the other hand,the WBC in the group whose dose was 4 times as that of intravenous chemotherapy was still low at the fifth day after intraperitoneal chemotherapy.Until the eighth day after chemotherapy,the WBC increased to the level of that before chemotherapy. Conclusions:The proper dose of topotecan would not damage the organs in peritoneal cavity.Intraperitoneal chemotherapy with topotecan might lead to the WBC of rats' peripheral blood decreased,and this change could recover shortly after chemotherapy.The intraperitoneal chemotherapy with topotecan would be safe in proper dose.It worth to begin clinical phase I trial.This will be the new strategy of the treatment to ovarian cancer,especially to advanced ovarian cancer,recurrent ovarian cancer and ovarian cancer resistant to carboplatin.