| 摘要: |
| 目的 应用超声联合血清学检测评估卡瑞利珠致乳腺癌大鼠心脏功能的损伤。方法 选取8~9周龄雌性SPF级SD大鼠32只，均于右侧腹股沟区皮下注射MADB-106大鼠乳腺癌细胞构建乳腺癌大鼠模型，并随机分为4组（对照组、标准剂量组、中等剂量组、高剂量组），每组8只。其中标准剂量组、中等剂量组、高剂量组每只大鼠分别连续腹腔注射卡瑞利珠单抗（溶于0.5 ml PBS缓冲液中）5 mg、10 mg、20 mg；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，每次注射时间为当天17:00-20:00。应用超声评估大鼠的心脏功能参数，包括左心室射血分数（LVEF）、左心室短轴缩短率（FS）、Tei指数。超声检查后于麻醉状态下经心脏负压采血2~10 ml，检测大鼠白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）、脑钠肽前体（NT-proBNP）及程序性死亡受体1（PD-1）抗体浓度。比较各组大鼠实验用药前后上述参数的差异。采血结束后，即刻解剖各组大鼠，计算其心脏脏器系数进行比较。结果 所有SD大鼠实验期间均存活，成瘤率为100%。对照组、标准剂量组及中等剂量组大鼠实验用药前后 LVEF、FS、Tei指数比较差异均无统计学意义；与实验用药前比较，高剂量组实验用药后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、中等剂量组、标准剂量组比较，高剂量组实验用药后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、标准剂量组及中等剂量组实验用药后IL-6、TNF-α及NT-proBNP比较差异均无统计学意义；与对照组、标准剂量组及中等剂量组比较，高剂量组实验用药后IL-6、TNF-α及NT-proBNP均升高，差异均有统计学意义（均P＜0.05）。与对照组、标准剂量组及中等剂量组比较，高剂量组实验用药后PD-1抗体升高，差异均有统计学意义（均P＜0.05）。实验用药后各组SD大鼠的心脏脏器系数比较差异无统计学意义。结论 卡瑞利珠可引起SD大鼠体内炎性反应，从而损伤心肌细胞导致心脏功能损伤，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的损伤情况。 |
| 关键词: 超声检查 血清学检测 心脏功能 卡瑞利珠 乳腺癌 SD大鼠 |
| DOI： |
| 投稿时间：2024-06-05修订日期：2024-08-18 |
| 基金项目: |
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| Ultrasonic diagnosis combined with serum ion to evaluate the cardiac function injury of breast cancer rats induced by Karelizhu |
| PAN Fuzhi,YE Dongman,ZHEN Huachuan,YU Tao |
| (Cancer Hospital of China Medical University/ Liaoning Cancer Hospital & Institute) |
| Abstract: |
| Objective This study aimed to assess the cardiac function injury in SD rats induced by Camrelizumab using a combination of ultrasonic diagnosis and serum biochemical indexes.Methods A total of 32 female SPF SD rats, aged 8-9 weeks, were selected to establish a breast cancer rat model through subcutaneous injection of MADB-106 rat breast cancer cells in the right groin area. The rats were randomly divided into four groups (control group, standard dose group, medium dose group, and high dose group), with eight rats in each group. Rats in the standard dose group, medium dose group, and high dose group 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 amount of PBS buffer for six consecutive times at intervals of 20 days between each injection from 17:00 to 20:00 on the same day. Cardiac function parameters including left ventricular ejection fraction (LVEF), left ventricular brachyaxis shortening rate (FS), and Tei index were evaluated using ultrasonography. After ultrasound examination, blood samples ranging from 2 to 10 ml were collected under cardiac negative pressure during anesthesia to measure interleukin-6 (IL-6) concentration, tumor necrosis factor-alpha (TNF-α) concentration, brain natriuretic peptide precursor (NT-proBNP) concentration and programmed death receptor-1(PD-1) antibody level. The above parameters were compared before and after experimental treatment within each group. After blood collection, the rats were immediately dissected for calculation of heart organ coefficients for comparison purposes..Results All SD rats survived and had a tumor formation rate of 100%. There were no significant differences observed in LVEF , FS ,and Tei indexes between pre-treatment measurements and post-treatment measurements within control groups as well as standard-dose groups or medium-dose groups . However, in high-dose groups, LVEF decreased, Fs decreased, and Tei index in control group, standard dose group and medium dose group before and after treatment. Compared with before experimental medication, LVEF and FS were decreased and Tei index was increased in high-dose group after experimental medication, with statistical significance (all P < 0.05). Compared with control group, medium dose group and standard dose group, LVEF and FS were decreased and Tei index was increased in high dose group after experimental treatment, and the differences were statistically significant (all P < 0.05). There was no significant difference in IL-6, TNF-α and NT-proBNP in control group, standard dose group and medium dose group. Compared with control group, standard dose group and medium dose group, IL-6, TNF-α and NT-proBNP in high-dose group were increased after experimental treatment, and the differences were statistically significant (all P < 0.05). Compared with control group, standard dose group and medium dose group, PD-1 antibody in high-dose group was increased after experimental treatment, and the differences were statistically significant (all P < 0.05). There was no significant difference in cardiac organ coefficients among all groups of SD rats.Conclusion After ultrasonic diagnosis and evaluation，combined with the change of serum biochemical ion concentration，Camrelizumab can cause inflammatory response in SD rats，thus damaging myocardial cells in SD rats，leading to cardiac function injury，and promoting the decline of cardiac function and motor function，in a dose-dependent manner，but does not affect the cardiac coefficient. |
| Key words: Ultrasound examination,Serological test,Cardiac function, Camrelizumab,Breast cancer,SD rats |
