摘要
目的 应用超声联合血清学检测评估卡瑞利珠单抗所致乳腺癌大鼠心脏功能损伤情况.方法 选取7～8周龄SPF级雌性SD大鼠32只,均于右侧腹股沟区皮下注射MADB-106大鼠乳腺癌细胞建立乳腺癌大鼠模型,并将其随机分为4组(对照组、A组、B组、C组),每组8只.其中A组、B组、C组大鼠分别腹腔注射卡瑞利珠单抗5 mg、10 mg、20 mg(溶于0.5 ml PBS缓冲液中);对照组大鼠腹腔注射等量PBS缓冲液,均连续注射6次,每次注射间隔20 d.应用超声检测实验用药前后大鼠心脏功能参数,包括左心室射血分数(LVEF)、左心室短轴缩短率(FS)、Tei指数.末次超声检查后于大鼠麻醉状态下经心脏负压采血2～10 ml,检测白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、脑钠肽前体(NT-proBNP)及程序性死亡受体1(PD-1)抗体浓度.比较各组大鼠上述参数的差异.采血结束后,即刻解剖各组大鼠,计算并比较心脏脏器系数.结果 所有大鼠实验期间均存活,成瘤率为100%.与实验用药前比较,C组实验用药后LVEF、FS均降低,Tei指数升高,差异均有统计学意义(均P<0.05);对照组、A组、B组实验用药前后LVEF、FS、Tei指数比较差异均无统计学意义.与对照组、A组、B组比较,C组实验用药后LVEF、FS均降低,Tei指数升高,差异均有统计学意义(均P<0.05).与对照组、A组、B组比较,C组IL-6、TNF-α、NT-proBNP及PD-1抗体浓度均升高,差异均有统计学意义(均P<0.05);对照组、A组、B组IL-6、TNF-α、NT-proBNP及PD-1抗体浓度比较差异均无统计学意义.各组大鼠心脏脏器系数比较差异无统计学意义.结论 卡瑞利珠单抗可导致乳腺癌大鼠心脏功能损伤,且存在剂量依赖性,但不会影响心脏脏器系数;应用超声联合血清学检测可以评估乳腺癌大鼠心脏功能损伤情况.
Abstract
Objective To assess the cardiac function damage induced by camrelizumab in rats with breast cancer using ultrasound combined with serological detection.Methods A total of 32 aged 7～8 weeks female SPF SD rats were subcutaneously injected with MADB-106 rat mammary carcinoma cells to establish a breast cancer model in the right inguinal region.The rats were randomly divided into four groups(control group,group A,group B,group C),with 8 rats in each group.Rats in the group A,B,C were successively injected with 5 mg,10 mg,and 20 mg of Camrelizumab(dissolved in 0.5 ml PBS buffer),respectively.Rats in the control group received intraperitoneal injections of the same dose of PBS buffer.All groups were injected 6 times consecutively,with an injection interval of 20 d.Cardiac function parameters before and after the administration of the experimental drugs,including left ventricular ejection fraction(LVEF),left ventricular brachyaxis fraction shortening(FS),and Tei index were detected by ultrasound.After the last ultrasound examination,blood samples ranging from 2 to 10 ml were collected under cardiac negative pressure during anesthesia to measure the concentrations of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),brain natriuretic peptide precursor(NT-proBNP)and programmed death receptor-1(PD-1)antibody.The differences of above parameters among the groups were compared.After the completion of blood collection,the rats in each group were dissected immediately,and the cardiac organ coefficients were calculated and compared.Results All SD rats survived during the experiment,and the tumor formation rate was 100%.Compared with the pre-experimental drug administration,the LVEF and FS in the group C were decreased after the administration of the experimental drug,while the Tei index was increased,and the differences were statistically significant(all P<0.05).There were no statistically significant differences in the LVEF,FS,and Tei index before and after the administration of the experimental drug among the control group,group A and group B.Compared with the control group,group A and group B,the LVEF and FS in the group C were decreased after the administration of the experimental drug,and the Tei index was increased,and the differences were statistically significant(all P<0.05).Compared with the control group,group A and group B,the concentrations of IL-6,TNF-α,NT-proBNP and PD-1 antibody in the group C were increased,and the differences were statistically significant(all P<0.05).There were no statistically significant differences in the concentrations of IL-6,TNF-α,NT-proBNP,and PD-1 antibody among the control group,group A and group B.There were no statistically significant differences in the cardiac organ coefficients among the groups.Conclusion Camrelizumab can induced cardiac function damage in SD rats,in a dose-dependent manner,but it does not affect the cardiac organ coefficient.The application of ultrasound combined with serological detection can assess the cardiac function damage in rats with breast cancer.
维普
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