1. 湖北省武汉市中西医结合医院中医科,湖北,武汉,430000
2. 上海中医药大学附属龙华医院肿瘤科,上海,200032
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罗琴琴, 徐振晔, 薛莎. 基于Blimp1/Bcl6通路探讨骨痛灵联合唑来膦酸治疗肺癌骨转移的实验研究[J]. 上海中医药杂志, 2018,52(12):84-89.
LUO Qinqin, XU Zhenye, XUE Sha. Experimental study on Gutongling Prescription combined with zoledronic acid in treating bone metastasis of lung cancer based on Blimp1/Bcl6 pathway[J]. Shanghai Journal of Traditional Chinese Medicine, 2018,52(12):84-89.
罗琴琴, 徐振晔, 薛莎. 基于Blimp1/Bcl6通路探讨骨痛灵联合唑来膦酸治疗肺癌骨转移的实验研究[J]. 上海中医药杂志, 2018,52(12):84-89. DOI: 10.16305/j.1007-1334.2018.12.022.
LUO Qinqin, XU Zhenye, XUE Sha. Experimental study on Gutongling Prescription combined with zoledronic acid in treating bone metastasis of lung cancer based on Blimp1/Bcl6 pathway[J]. Shanghai Journal of Traditional Chinese Medicine, 2018,52(12):84-89. DOI: 10.16305/j.1007-1334.2018.12.022.
目的:观察骨痛灵方对肺癌骨转移疼痛模型小鼠Blimp1/Bcl6通路的影响。 方法:85只C57 BL/6小鼠随机选取17只小鼠,注射PBS溶液作为假手术组;其余68只小鼠左后肢胫骨骨髓腔内注射Lewis肺癌细胞建立骨转移疼痛模型,随机分为模型组、中药组、西药组、中西药组,每组17只。中药组小鼠以骨痛灵方煎剂灌胃,西药组予以唑来膦酸腹腔注射,中西药组则两药联合运用,治疗3周。采用TRAP特殊染色法检测小鼠胫骨的破骨细胞,以RT-PCR和Western blot法检测B细胞诱导成熟蛋白1(Blimp1)、B细胞淋巴瘤蛋白6(Bcl6)和组织蛋白酶K(Ctsk)mRNA和蛋白的表达。 结果:与模型组比较,中药组、西药组和中西药组TRAP阳性细胞数量均明显减少,Blimp1、Ctsk mRNA和蛋白表达均降低,Bcl6 mRNA和蛋白表达均升高,且差异均有统计学意义(P<0.05);在3个治疗组中,中西药组阳性细胞数量最少,Blimp1、Ctsk mRNA和蛋白表达最低,Bcl6 mRNA和蛋白表达最高,差异有统计学意义(P<0.05)。 结论:骨痛灵方通过抑制Blimp1/Bcl6通路,抑制破骨细胞的活化,从而缓解肺癌骨转移疼痛。
Objective:To observe the effects of Gutongling Prescription on the Blimp1/Bcl6 pathway in the mouse pain model of bone metastasis of lung cancer. Methods85 C57BL/6 mice were selected. Among, 17 mice were taken as the sham operation group, which treated with PBS solution. The pain model of bone metastasis of lung cancer was established in the other 68 mice by injecting Lewis cells suspension into the left hind tibia medullary cavity. Then the model mice were randomly divided into the model group, Chinese medicine group, western medicine group, Chinese and western medicine combination group, 17 mice in each group. The Chinese medicine group was treated with decoction of Gutongling Prescription by intragastric administration, the western medicine group was treated with zoledronic acid by intraperitoneal injection, and the Chinese and western medicine combination group was treated with decoction of Gutongling Prescription and zoledronic acid, with a course of 3 weeks. The osteoclasts of tibia in mice were detected by TRAP staining. The mRNA and protein expressions of B lymphocyte induced maturation protein1(Blimp1), B-cell lymphoma 6(Bcl6) and cathepsin K(Ctsk) were detected by RT-PCR and Western Blot. Results:Compared with the model group, the number of TRAP positive cells was decreased remarkably in the Chinese medicine group, western medicine group and Chinese and western medicine combination group, and the mRNA and protein expressions of Blimp1 and Ctsk were reduced, while the mRNA and protein expressions of Bcl6 were increased, with statistically significant differences (P<0.05). Among the three drug treatment groups, the Chinese and western medicine combination group showed the least number of positive cells, the lowest mRNA and protein expressions of Blimp1 and Ctsk and the highest mRNA and protein expressions of Bcl6, with statistically significant differences (P<0.05). Conclusion:Gutongling Prescription can suppress the osteoclast activation by inhibiting Blimp1/Bcl6 pathway, and thus alleviate the pain induced by bone metastasis of lung cancer.
肺癌骨转移破骨细胞B细胞诱导成熟蛋白1B细胞淋巴瘤蛋白6组织蛋白酶K
bone metastasis of lung cancerosteoclastBlimp1Bcl6Ctsk
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