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目的观察肝动脉灌注碘油羟基磷灰石纳米粒(nHAP)对兔 VX2肝肿瘤生长、坏死率、凋亡指数、微血管密度(MVD)及增殖细胞核抗原(PCNA)表达的影响,同时观察其对瘤兔生存期的影响。方法 80只新西兰白兔肝内肿瘤种植后2周,随机分为4组,每组20只,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,实验设生理盐水组(A 组)、单纯碘油组(B 组)、阿霉素碘油组(C 组)及碘油 nHAP 组(D 组)。治疗后1周及2周,采用 CT 检测肿瘤大小,计算肿瘤的生长率。治疗后2周,病理观察肿瘤区的坏死率,DNA 缺口末端标记(TUNEL)法检测肿瘤的凋亡指数,免疫组化方法测定肿瘤的 MVD 值。记录各组实验兔治疗后的存活期。结果治疗后1、2周,碘油nHAP 组肿瘤体积及生长率明显小于其他各组(均 P<0.05)。治疗后2周,碘油 nHAP 组肿瘤坏死率和凋亡指数大于其他各组(均 P<0.05)。单纯碘油组及阿霉素碘油组栓塞后,残余肿瘤区的 MVD(条)升高,两者分别为34±7和35±8,高于阴性对照 A 组(23±6,P<0.05);碘油 nHAP 组残余瘤区MVD(16±4)条低于其他组。栓塞组增殖指数低于阴性对照 A 组,碘油 nHAP 组增殖指数低于其他各组(均 P<0.05)。4组瘤兔治疗后的生存天数(d)分别为38±6、46±8、50±8、55±9。碘油 nHAP 组治疗后的生存期长于其他组(均 P<0.05)。结论肝动脉灌注碘油 nHAP 可明显抑制肿瘤生长,延长瘤兔的生存期,其可能通过促进肿瘤细胞坏死、诱导肿瘤细胞凋亡、抑制肿瘤细胞增殖和抑制肿瘤血管生成发挥抗肿瘤效应。
Objective To observe the effect of hepatic artery lipiodol hydroxyapatite nanoparticles (nHAP) on the growth, necrosis rate, apoptosis index, microvessel density (MVD) and PCNA expression of VX2 liver tumor in rabbits. The impact of tumor survival in rabbits. Methods Eighty New Zealand white rabbits were divided into 4 groups at random after 2 weeks of implantation. The rabbits in the middle of the upper abdomen were laparotomy, the gastroduodenal artery was cannulated and fixed, Saline group (group A), lipiodol group (group B), doxorubicin lipiodol group (group C) and lipiodol nHAP group (group D). One week and two weeks after treatment, the tumor size was calculated by CT, and the growth rate of the tumor was calculated. Two weeks after the treatment, necrosis rate of the tumor area was observed by pathology, apoptosis index was detected by TUNEL method, and MVD value was measured by immunohistochemistry. Record the survival of rabbits in each group after treatment. Results After 1 and 2 weeks of treatment, the tumor volume and growth rate in nHAP group were significantly lower than those in other groups (all P <0.05). Two weeks after treatment, the tumor necrosis rate and apoptosis index in nHAP group were higher than those in other groups (all P <0.05). After embolization of the lipiodol group and the doxorubicin lipiodol group, the MVD of the residual tumor area was increased (34 ± 7 and 35 ± 8, respectively), which was higher than that of the negative control group A (23 ± 6, P < 0.05). MVD (16 ± 4) in residual tumor area of nHAP group was lower than other groups. The proliferation index of embolism group was lower than that of negative control group A, while the proliferation index of nHAP group was lower than that of other groups (all P <0.05). The survival days of the four groups of tumor rabbits (d) were 38 ± 6,46 ± 8,50 ± 8,55 ± 9, respectively. The survival rate of nHAP group was longer than that of other groups (all P <0.05). Conclusion Hepatic artery perfusion of lipiodol nHAP can significantly inhibit tumor growth and prolong survival of tumor-bearing rabbits. It may play an antitumor effect by promoting tumor cell apoptosis, inducing tumor cell apoptosis, inhibiting tumor cell proliferation and inhibiting tumor angiogenesis.