精元康胶囊对齐多夫定致骨髓抑制小鼠骨髓Notch信号通路的影响

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目的:观察精元康胶囊对齐多夫定(azidothymidine,AZT)所致骨髓抑制小鼠骨髓Notch信号通路中jag1 mRNA、numb1 mRNA和numb2 mRNA表达情况的影响,探究精元康胶囊治疗骨髓抑制相关作用机制。方法:选用SPF级雄性昆明种小鼠70只,按照随机数字表法分为空白对照组(简称空白组)、模型组、利可君片组(简称利可君组)、贞芪扶正胶囊组(简称贞芪组)、精元康胶囊高剂量组(简称精高组)、精元康胶囊中剂量组(简称精中组)、精元康胶囊低剂量组(简称精低组),每组10只,分别给予不同药物处理,连续14 d。断颈处死小鼠,分离右股骨,制备骨髓单细胞悬液,运用实时荧光定量PCR法检测Notch信号通路中jag1 mRNA、numb1 mRNA和numb2 mRNA的表达情况。结果:(1)与空白组比较,小鼠经AZT造模后,模型组及各药物组Notch信号通路中jag1 mRNA表达明显升高(P<0.05)。与模型组比较,各药物组jag1 mRNA表达水平均明显下降(P<0.05)。精高组、精中组效果明显优于贞芪组、利可君组(P<0.05),而精低组、利可君组、贞芪组3组之间无显著差异(P>0.05)。(2)与空白组比较,模型组及各药物组numb1 mRNA表达明显降低(P<0.05)。与模型组比较,各药物组numb1 mRNA表达水平均明显升高(P<0.05)。精高组、精中组numb1 mRNA表达水平明显高于贞芪组、利可君组(P<0.05),而精低组numb1 mRNA表达水平低于利可君组、贞芪组。(3)与空白组比较,模型组及各药物组numb2 mRNA表达明显降低(P<0.05)。与模型组比较,各药物组numb2 mRNA表达水平均明显升高(P<0.05)。精高组numb2 mRNA表达水平明显高于贞芪组、利可君组(P<0.05),精中组numb2 mRNA表达水平与贞芪组、利可君组相当(P>0.05),而精低组numb2 mRNA表达量低于利可君组、贞芪组。结论:精元康胶囊可下调骨髓抑制小鼠增高的jag1 mRNA的表达量,同时使原本降低的numb1 mRNA、numb2 mRNA的表达升高,使激活的Notch信号通路得到抑制,进而促进骨髓造血功能的恢复,且呈现剂量依赖性。 Objective: To observe the effect of Jingyuankang on the expression of jag1 mRNA, numb1 mRNA and numb2 mRNA in bone marrow of bone marrow of mice with bone marrow suppression induced by azidothymidine (AZT), and to explore the mechanism of Jingyuankang capsule in the treatment of myelosuppression. Methods: Seventy male Kunming SPF mice were randomly divided into blank control group (model group), model group, Li Ke Jun Tablet (Li Ke Jun) (Shenqi group), Jingyuan Kang capsule high dose group (sperm group), Jingyuankang capsule middle dose group (shenzhong group) and Jingyuankang capsule low dose group (sperm group) , Were given different drug treatment, continuous 14 d. Mice were sacrificed and the right femur was isolated to prepare bone marrow single cell suspension. The expression of jag1 mRNA, numb1 mRNA and numb2 mRNA in Notch signaling pathway was detected by real-time fluorescence quantitative PCR. Results: (1) Compared with the blank group, the expression of jag1 mRNA in Notch signaling pathway of model group and each drug group was significantly increased (P <0.05). Compared with model group, the expression of jag1 mRNA in each drug group decreased significantly (P <0.05). (P <0.05), while there was no significant difference between the three groups in the Jingjing group, the Li Kejun group and the Zhenqi group (P> 0.05) . (2) Compared with the blank group, the expression of numb1 mRNA in model group and each drug group decreased significantly (P <0.05). Compared with the model group, the expression of numb1 mRNA in each drug group was significantly increased (P <0.05). The levels of numb1 mRNA in the Jingao and Jingzhong groups were significantly higher than those in the Zhenqi group and the Li Kejun group (P <0.05), while the levels of numb1 mRNA in the Jingjing group and the Zhijing group were lower than those in the Liqijun and Zhenqi groups. (3) Compared with the blank group, the expression of numb2 mRNA in model group and each drug group decreased significantly (P <0.05). Compared with the model group, the expression of numb2 mRNA in each drug group was significantly increased (P <0.05). The expression level of numb2 mRNA in the seminal plasma was significantly higher than that in the ZhenQi and liKeJun groups (P <0.05). The numb2 mRNA expression level in the seminal plasma group was similar to those in the ZhenQi and liKeJun groups (P> 0.05) The mRNA expression level was lower than that of Richen group and Zhenqi group. CONCLUSION: Jing Yuan Kang Capsule can down-regulate the expression of jag1 mRNA in myelosuppressed mice and increase the expression of numb1 mRNA and numb2 mRNA, and inhibit the activation of Notch signaling pathway, thereby promoting the recovery of bone marrow hematopoietic function , And showed dose-dependent.
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