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NSG小鼠多发性骨髓瘤模型评价BCMA-CAR-T的药效和毒性及RNAscop在检测CAR-T分布中的应用 被引量:1
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作者 荣斌 吴纯启 +6 位作者 原野 尹纪业 瞿文生 李晓旭 范丹 贺小琼 王全军 《药物评价研究》 CAS 2019年第5期822-827,共6页
目的选择合适的小鼠模型,评价以B细胞成熟抗原为靶点的嵌合抗原受体T细胞(BCMA-CAR-T)治疗产品的抗多发性骨髓瘤作用及毒性,探讨RNAscope在CAR-T治疗中的应用。方法在免疫缺陷严重的NSG小鼠中建立MM. 1s-luc多发性骨髓瘤模型,随机分为... 目的选择合适的小鼠模型,评价以B细胞成熟抗原为靶点的嵌合抗原受体T细胞(BCMA-CAR-T)治疗产品的抗多发性骨髓瘤作用及毒性,探讨RNAscope在CAR-T治疗中的应用。方法在免疫缺陷严重的NSG小鼠中建立MM. 1s-luc多发性骨髓瘤模型,随机分为细胞外液组(每只小鼠100μL PBS缓冲液)、MOCK-T组(未转染的T细胞,剂量为100μL)和CAR-T低、中、高剂量组(分别每只计数1×10~6、5×10~6、10×10~6个CAR-T,每只一次性尾iv 100μL细胞悬液)。采用活体成像技术检测CAR-T治疗肿瘤的消退效果;酶联免疫吸附实验检测血浆中γ-干扰素(IFN-γ)水平;观察小鼠一般状态、体温、体质量;治疗后14 d对小鼠进行解剖和采样,利用RNAscope技术检测CAR-T在小鼠组织的特异性分布。结果成功建立了多发性骨髓瘤NSG小鼠移植肿瘤模型;在输注BCMA-CAR-T后3、7、12 d,生物发光成像显示,CAR-T组小鼠平均光子强度显著低于细胞外液、MOCK-T组(P<0.05),中、高剂量组的治疗效果明显高于低剂量组(P<0.05);CAR-T组的IFN-γ分泌水平显著高于细胞外液、MOCK-T组(P<0.05);记录CAR-T治疗组小鼠的一般情况,未见明显不良反应;RNAscope检测到CAR-T在输注14 d后少量特异性分布于骨髓和脾脏。结论本研究验证了BCMA-CAR-T抗多发性骨髓瘤药效明显,安全可靠,RNAscop技术可应用于CAR-T分布检测。 展开更多
关键词 BCMA-CAR-T 多发性骨髓瘤 生物发光成像 药效 毒性 RNAscope γ-干扰素
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Chemical characters and protective effect of Baqi Lingmao formula(巴芪灵猫方) on experimental liver injury
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作者 LIU Lulu CHEN Yanxu +10 位作者 LIU Lulu LI Man XU Rui QU Wensheng yin jiye ZHANG Xin ZHOU Zhenhua GAO Yating NIE Dan SHAN Junjie GAO Yueqiu 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2021年第6期862-874,共13页
OBJECTIVE:To investigate the chemical characters of water-extract of Baqi Lingmao formula(巴芪灵猫方,BQLM formula)and its effects on anti-liver injury in model mice and live cells.METHODS:BQLM formula was composed of ... OBJECTIVE:To investigate the chemical characters of water-extract of Baqi Lingmao formula(巴芪灵猫方,BQLM formula)and its effects on anti-liver injury in model mice and live cells.METHODS:BQLM formula was composed of ten herbal medicines.We determined the contents of alkaloids,saponins,phenolic acids and flavonoid in BQLM formula by UV spectrophotometry.The active components of alkaloids and phenolic acids in BQLM formula were identified by HPLC chromatography.The anti-hepatic injury effects of BQLM formula were investigated with concanavalin A(Con A)-induced hepatitis model of mice,human liver LO2 and Hep G2.2.15 cells.RESULTS:BQLM formula(2 and 10 g/kg,orally)significantly improved the damages of liver tissues and functions caused by Con A in mice,reduced the infiltration of inflammatory cells into liver and inhibited the inflammatory cytokine secretion of interferon-γ,tumor necrosis factor-αand interleukin-6.BQLM formula simultaneously decreased the levels of alanine aminotransferase and aspartate aminotransferase of liver and serum,and recovered the superoxide dismutase and catalase activities of liver to normal levels in Con A-induced hepatic-injury mice.The serum of BQLM formula group stimulated the human liver LO2 cell proliferation in vitro.Further,BQLM formula obviously promoted the proliferation of normal hepatocytes(LO2 cells)and inhibited the hepatocytes death induced by Con A.It also significantly inhibited the proliferation of Hep G2.2.15 cells and decreased the secretion of HBs Ag and HBe Ag in vitro.CONCLUSIONS:BQLM formula has anti-inflammation and anti-hepatitis virus Beffects,and is capable of improving liver injury in vivo and in vitro. 展开更多
关键词 hepatitis B chronic concanavalin A injury HEPATOCYTES Baqi Lingmao formula
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