多靶点酶抑制剂？清燥救肺汤调控水形态影响肺癌细胞能量代谢的“清热润燥”机制研究

Chinese herbal compound recipe is a unique form of drug application in China, because of its characteristics of multiple components and multiple targets to deal with the complexity of the disease and show a unique effect. Although great progress has been made in the study of compound multi-component, the research on multi target is still not deep enough. Early,according to dry heat impairing lung characteristics of lung tumor, we researched on decoction for reliving dryness of the lung as representative prescriptions and confirmed it could significantly inhibit the proliferation of lung cancer and increased the combined with water of lung tumor cell. The research group referenceed the modern scientific research "closely related to water and energy metabolism in cell morphology, with more water, the hydrogen can make the active center of enzyme conformation is not easy to change form, not with substrate binding, resulting in decreased enzyme activity, energy metabolism was weakened” and put forward the scientific hypothesis" decoction for reliving dryness of the lung is a multi target enzyme inhibitor.It moistening lung cancer cells increased with bound water content, and inhibit the energy metabolism enzyme activity, relieve dry heat and moistening lung cancer suppressor effect",and detect the changes speed limit enzyme activities and metabolites in the pathway of energy metabolism of lung cancer cells, further clear the "heat" the mechanism and targets,provide the reference for the scientific connotation of "lung heat and moistening therapy" and new ideas for the traditional Chinese medicine research on multi-target anti-tumor.

中药复方是我国特有的药物应用形式，因其多成分多靶点的特点，应对复杂性疾病显示了独特的疗效。虽然目前对复方多成分研究取得很大进展，但对多靶点研究仍不够深入。前期我们根据肺癌燥热伤肺发病特点，对清热润燥代表方清燥救肺汤展开研究，证实该方能显著抑制肺癌增殖，并能增加肺癌细胞结合水含量。课题组借鉴“水形态与能量代谢密切相关，细胞内结合水越多，其氢键可使酶活性中心空间构象不易改变，无法与底物结合，致使酶催化活性降低，能量代谢减弱”的现代科研成果，提出“清燥救肺汤是多靶点酶抑制剂，它通过‘润燥’增加肺癌细胞结合水含量，‘清热’抑制其能量代谢限速酶活性，达到缓解肺癌燥热的‘清热润燥’抑癌功效”科学假说，并拟通过检测肺癌细胞各能量代谢途径限速酶活性及中间代谢产物变化，进一步明确该方的“清热”机制及作用靶点，为诠释肺癌“清热润燥”治法科学内涵提供参考，为中药多靶点抗肿瘤研究提供新思路。

肺癌常有干咳少痰，痰中带血，声音嘶哑等燥热伤肺表现，放化疗后更为明显。患者虽采取西医放化疗等综合治疗手段，死亡率仍高居恶性肿瘤首位。抑制肺癌增殖同时又能缓解肺癌燥热是临床亟需解决的实际问题。.清燥救肺汤为清代名医喻嘉言清热润燥代表方，主治燥热伤肺重症，与肺癌燥热病机相符，能较好地缓解燥热伤肺主症，故常用于肺癌临床治疗中并为名老中医推崇。但该方抗肺癌机制尚属空白。.为此，我们展开前期研究，证实该方能显著抑制肺癌细胞增殖，，但其缓解肺癌燥热的机制尚不清楚。课题组从“润燥”功效出发，研究了该方对肺癌细胞内水的影响，结果表明，清燥救肺汤能显著增加肺癌细胞内结合水的含量。.课题组借鉴“水的形态与能量代谢密切相关，细胞内结合水越多，其氢键可使酶活性中心的空间构象不易改变，无法与底物结合，致使酶催化活性降低，能量代谢减弱”的现代科研成果，提出“清燥救肺汤是多靶点酶抑制剂，它通过润燥增加肺癌细胞结合水含量，清热抑制其能量代谢限速酶活性，达到缓解肺癌燥热的清热润燥抑癌功效”科学假说，并通过检测肺癌细胞糖酵解、磷酸戊糖、三羧酸循环、氧化磷酸化等能量代谢途径限速酶表达及中间代谢产物变化，进一步明确该方抗肺癌的“清热”机制及作用靶点。.中药复方是我国特有的药物应用形式，因其多成分多靶点的特点，应对复杂性疾病，显示了独特的疗效。虽然目前对复方多成分研究取得很大进展，但对多靶点研究仍不够深入。本课题尝试从多靶点酶抑制剂角度探索清燥救肺汤“清热润燥”抗肺癌机制，为中药多靶点抗肿瘤研究提供新思路。.目前为止，课题组已完成课题投计的全部实验内容，并证实清热润燥经方清燥救肺汤能显著抑制肺癌细胞增殖，其机理可能是通过抑制癌细胞糖酵解、磷酸戊糖、三羧酸循环、氧化磷酸化代谢途径限速酶活性，阻止癌细胞利用糖原脂类蛋白质，从而发挥“清热”抑制肺癌细胞能量代谢功效而实现的。