不同剂量的羟基磷灰石纳米微粒治疗兔肝VX2肿瘤的实验研究

目的研究不同剂量的羟基磷灰石纳米微粒(hydroxyapatitenanoparticle,nHAP)对兔肝VX2肿瘤的治疗作用。方法将60只新西兰白兔经肝内肿瘤种植2周后随机分成4组,每组15只。于兔上腹正中开腹,胃十二指肠动脉插管固定,经肝动脉灌注给药。A组为生理盐水(5ml)对照组;B组为低剂量nHAP组,肝动脉注入nHAP(0.5mg/kg);C组为中剂量nHAP组,肝动脉注入nHAP(5mg/kg);D组为高剂量nHAP组,肝动脉注入nHAP(50mg/kg)。4组实验动物分别于治疗前,治疗后7d、14d行SCT肝脏扫描,测量肿瘤的大小,并计算肿瘤生长率。治疗前,治疗后1d、7d行血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)检测。各组实验动物均记录治疗后的生存天数。结果治疗后7d、14d,中剂量nHAP组和高剂量nHAP组的肿瘤体积和生长率都小于生理盐水对照组,有显著性差异(P<0.05);低剂量nHAP组与对照组相比无统计学差异(P>0.05);中剂量nHAP组与同期高剂量nHAP组相比,无显著性差异(P>0.05)。术后1d,D组血清AST、ALT均升高,与对照组相比差异有统计学意义(P<0.05)。术后7d,D组AST、ALT降至正常。治疗后,A、B、C组AST、ALT均未升高。A、B、C、D组瘤兔治疗后生存期分别为(38.0±5.4)d、(39.5±6.6)d、(45.2±7.7)d、(45.6±8.2)d,C、D两组与对照组相比有显著性差异(P<0.05)。结论在一定剂量范围内,nHAP对兔肝VX2肿瘤的生长具有抑制作用,并能提高瘤兔的生存期,其肝功能损害是可逆的。

Experimental study of different doses of hydroxyapatite nanoparticles treating liver VX2 tumor in rabbits

Objective To study the effects of hydroxyapatite nanoparticle(nHAP)at different dosages on liver tumor growth in rabbits. Methods Sixty New Zealand white rabbits were randomly divided into 4 groups,each having 15 rabbits, and VX2 carcinoma was implanted in the left lobes of the liver.Two weeks later,a catheter was inserted into the gastroduodenal artery of the rabbit and nHAP at different dosages were injected into rabbits via hepatic artery.The rabbits in group A(control group)were injected with 5ml saline,those in group B with low dose of nHAP( 0.5 mg/kg),those in group C with middle dose of nHAP(5 mg/kg),and those in group D with high dose of nHAP(50 mg/kg).Spiral CT scan was performed to measure tumor volume 7 and 14 days after treatment.The serum levels of AST and ALT were determined on the day 1 and 7 after treatment.The survival of VX2 rabbits after treatment was also recorded. Results The tumor growth rate in groups C and D on the day 7 and 14 after treatment was lower than that in control group(P< 0.05 ),but there was no significant difference between group B and control group.The life span of group C or group D was longer than that in control group(P< 0.05 ),while there was no significant difference between group B and control group(P> 0.05 ).The serum level of AST or ALT in group D was higher than that in the other three groups on the first day after treatment(P< 0.05 ),but the serum level of AST or ALT was normal in all groups on the 7th day after treatment.Conclusion nHAP(5 to 50 mg/kg)has significant inhibitory effect on liver VX2 tumor growth in rabbits with minimal liver toxicity,and can prolong the life span of the rabbits with VX2 liver tumors.