奥曲肽对二乙基亚硝胺诱导的大鼠肝癌的影响

Effects of octreotide on DENA induced murine liver cancer

目的研究生长抑素类似物奥曲肽（octreotide，OCT）抑制大鼠诱导肝癌形成的效果及其机制。方法用二乙基亚硝胺溶液（DENA）诱导大鼠肝癌模型，随机分成OCT治疗组和对照组，观察两组大鼠存活情况和肝癌发生率，用免疫组化和半定量RT—PCR的方法检测肝脏和肝癌组织中生长抑素受体2（somatostatin receptor2，SSTR2）蛋白和mRNA的水平。结果OCT组的存活率70．0％（7／10）明显高于对照组30．0％（6／20）（X^2=4．344，P〈0．05）；DENA喂养16周的诱癌率，OCT组（0％，0／10）低于对照组（30．0％，6／20），但两组比较差异无统计学意义（X^2=3．750，P〉0．05）；DENA喂养22周的诱癌率，OCT组（22．2％，2／9）显著低于对照组（83．3％，10／12）（X^2=7．843，P〈0．01）。SSTR2mRNA和蛋白表达随肝硬化加重而增加，DENA喂养16周时最强，DENA喂养22周时明显下降，肝癌内的表达更低于周边组织（分别F=35．010和13．386，均P〈0．01）；OCT治疗组DENA喂养8周和16周后的SSTR2 mRNA和蛋白水平均近似于对照组，但DENA喂养22周时两者的水平均无明显下降，明显高于同期对照组（分别t=2．806和4．498，均P〈0．05）。结论OCT能有效地抑制大鼠肝癌的形成，并减少诱癌大鼠的死亡率，SSTR2表达的维持可能是OCT发挥作用的关键。

Objective To investigate the effect and mechanism of octreotide （OCT） on DENA related hepatocarcinogenesis in rats. Methods Fresh diethylnitrosamine （DENA） solution was given to induce the model of rat hepatocellular carcinoma. The rats were divided randomly into two groups： OCT treatment group and control group. The survival rate and hepatocarcinogenesis rate were observed. SSTR2 mRNA and protein expression were measured. Results The survival rate of OCT treatment group （70. 0%, 7/10） was significantly higher than that of control group （ 30.0%, 6/20） （X^2 = 4. 344, P 〈 0. 05）. 16 weeks after DENA treatment, the difference of hepatocarcinogenesis rate between the two groups was not remarkable though the value of OCT treatment group （0% , 0/10） was lower than that of control groups （ 30. 0% , 6/20） （ X^2 = 3. 750, P 〉 0.05 ）. However, 22 weeks after DENA treatment, hepatocarcinogenesis in control group （ 83.3% , 10/12 ） was markedly higher than that in OCT treatment group （22. 2%, 2/9 ） （ X^2 = 7. 843, P 〈 0.01 ）. With liver cirrhosis progressing, the expressions of SSTR2 mRNA and protein increased, and reached the peak 16 weeks after DENA treatment, then began to decrease. The expressions of SSTR2 mRNA and protein in hepatocellular carcinoma were significantly lower than those in the liver 22 weeks after DENA treatment （ F = 35. 010 and 13. 386, P 〈 0. 01 ）. The expression levels in OCT treatment group were similar to those in control group 8 and 16 weeks after DENA treatment. But the expression levels in OCT group 22 weeks after DENA treatment didn＇t lower markedly, and were higher significantly than those in control group （t = 2. 806 and 4. 498, P 〈 0.05）. Conclusion OCT can inhibit efficiently hepatocarcinogenesis and reduce the mortality of rats treated with DENA possibly by a mechanism maintaining the expression levels of SSTR2.