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护肝布祖热方联合奥沙利铂对肝细胞癌荷瘤裸鼠的减毒增效作用及机制
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| 篇名： | 护肝布祖热方联合奥沙利铂对肝细胞癌荷瘤裸鼠的减毒增效作用及机制 |
| TITLE： | Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism |
| 摘要： | 目的 研究护肝布祖热方联合奥沙利铂对肝细胞癌荷瘤裸鼠的减毒增效作用及机制。方法从40只裸鼠中选取8只作为空白组（生理盐水），其余32只裸鼠皮下接种人肝癌Huh7细胞构建荷瘤裸鼠模型。将造模成功的32只裸鼠随机分为模型组（生理盐水，灌胃）、奥沙利铂组（10mg/kg，腹腔注射）、护肝布祖热方组（0.69g/kg，灌胃）和联合用药组（腹腔注射10mg/kg奥沙利铂+灌胃0.69g/kg护肝布祖热方浸膏），每组8只。每天灌胃给药/生理盐水1次，连续32d；每7天腹腔注射给药1次，共5次。实验期间，观察各组裸鼠一般情况，每4d测量1次肿瘤体积；给药第30天，检测裸鼠热刺激缩足潜伏期；给药结束后，检测各组裸鼠的抑瘤率、脾脏系数、血常规指标以及血清中天冬氨酸转氨酶（AST）和肌酐水平，观察裸鼠肿瘤组织病理形态变化，检测肿瘤组织中微管相关蛋白1轻链3（LC3）、选择性自噬接头蛋白p62、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）和胱天蛋白酶3（Caspase-3）的表达。结果与模型组比较，奥沙利铂组裸鼠肿瘤体积、瘤重以及全血中白细胞、红细胞数量和脾脏系数均显著减小/降低（P＜0.01），热刺激缩足潜伏期和血清中AST、肌酐水平均显著延长/升高（P＜0.05或P＜0.01）。与奥沙利铂组比较，联合用药组裸鼠肿瘤体积、瘤重均显著减小/降低（P＜0.01），全血中白细胞、红细胞、血小板数量和脾脏系数均显著增加/升高（P＜0.05或P＜0.01），热刺激缩足潜伏期和血清中AST、肌酐水平均显著缩短/降低（P＜0.01）；肿瘤组织中LC3、Bax和Caspase-3蛋白的表达水平均显著升高（P＜0.01），p62、Bcl-2蛋白的表达水平均显著降低（P＜0.01）。结论护肝布祖热方通过诱导凋亡和自噬增强奥沙利铂对裸鼠的抑瘤作用，并可缓解奥沙利铂引起的外周神经毒性、血液毒性、肝肾毒性和免疫器官毒性。 |
| ABSTRACT： | OBJECTIVE To investigate the attenuation and synergism of Hugan buzure recipe （HBR） combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism. METHODS Eight nude mice were selected from 40 nude mice as the blank group （normal saline）， and the remaining nude mice were inoculated with hepatoma cells Huh7 to establish the tumor-bearing model. The 32 modeled nude mice were randomly allocated to four groups： model group （normal saline， ig）， HBR group （0.69 g/kg， ig）， oxaliplatin group （10 mg/kg， ip）， and combination group （intraperitoneal injection of 0.69 g/kg HBR+intragastric administration of 10 mg/kg oxaliplatin）， with 8 mice in each group. Administer drug/normal saline once a day for 32 consecutive days； administer subcutaneous injection once every 7 days for a total of 5 times. During the experiment， the general condition of nude mice in each group was observed， and the tumor volume was measured every 4 days. On the 30th day of administration， the thermal stimulation paw withdrawal latency of nude mice in each group were detected. The tumor inhibition rate， spleen coefficient， the number of red blood cells， white blood cells and platelets in the whole blood of nude mice in each group， and the content of aspartate aminotransferase （AST） and creatinine in serum were detected after the end of administration. HE staining was used to observe the pathological changes in tumor tissues in nude mice in each group. The expression of microtubule-associated protein 1 light chain 3 （LC3），selective autophagy adaptor protein p62， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Caspase-3 protein in tumor tissues. RESULT Compared with the model group， the tumor volume， tumor weight， white blood cells，red blood cells in the whole blood and spleen coefficients of nude mice in the oxaliplatin group were significantly decreased （P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly increased （P＜0.05 or P＜0.01）. Compared with the oxaliplatin group， the tumor volume and tumor weight of nude mice in the combination group were significantly decreased （P＜0.01）； the white blood cells， red blood cells and platelets in the whole blood and spleen coefficients of nude mice were significantly increased （P＜0.05 or P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly decreased （P＜0.01）； the expression levels of LC3， Bax and Caspase-3 proteins in tumor tissues of nude mice were significantly increased （P＜0.01）， and the expression levels of p62 and Bcl-2 proteins were significantly decreased （P＜0.01）. CONCLUSIONS HBR enhances the tumor inhibition rate of oxaliplatin by inducing apoptosis and autophagy， and can alleviate the peripheral neurotoxicity， hematological toxicity， hepatorenal toxicity， and immune organ toxicity caused by oxaliplatin in nude mice. |
| 期刊： | 2024年第35卷第03期 |
| 作者： | 孟小艺；杨建华；文丽梅；阿依孜巴·图尔洪；胡君萍 |
| AUTHORS： | MENG Xiaoyi，YANG Jianhua，WEN Limei，Ayiziba·Tuerhong，HU Junping |
| 关键字： | 护肝布祖热方；奥沙利铂；肝癌；减毒增效；凋亡；自噬 |
| KEYWORDS： | Hugan buzure recipe； oxaliplatin； hepatic cancer； attenuation and synergism； apoptosis； autophagy |
| 阅读数： | 148 次 |
| 本月下载数： | 63 次 |
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