MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats.
MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats.
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MASM 是一种苦参碱衍生物，通过调节 Wistar 大鼠致死性全身辐射诱导的多信号通路提供辐射防护
DOI：
10.3390/molecules21050649
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发表时间：
2016-05-17
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Li J;Xu J;Lu Y;Qiu L;Xu W;Lu B;Hu Z;Chu Z;Chai Y;Zhang J
苦参碱是从苦参中提取的生物碱，具有抗炎、抗肿瘤、抗纤维化、免疫抑制等多种生物活性。在我们以前的研究中，我们合成了苦参碱衍生物MASM，并显示了很强的抗肝纤维化活性。本研究主要研究其对大鼠致死性全身照射(TBI)的防护作用。在致死性脑损伤前后应用MASM可减少大鼠的放射病症状，增加大鼠30天的存活时间。超微结构观察显示，MASM对照射大鼠不同脏器的超微结构损伤有明显的保护作用。基因表达谱显示，MASM预处理对脑损伤后基因表达的改变有显著影响。MASM可抑制脑损伤诱导的1445个差异表达基因中的53%(765个基因)的差异表达。途径丰富分析表明，这些基因主要涉及代谢途径、肿瘤中的途径和丝裂原活化蛋白激酶(MAPK)途径等21条途径。提示MASM对致死性脑损伤的保护作用可能主要或部分是通过对这些通路的调节，如多条MAPK通路。因此，MASM有可能成为一种有效的治疗或放射防护剂，以最大限度地减少辐射损伤，并与放射治疗相结合，提高癌症治疗的疗效。
Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI) in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes) of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK) pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.
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影响因子：
3.7
作者：
Fukumoto R;Burns TM;Kiang JG
通讯作者：
Kiang JG
影响因子：
11.2
作者：
Gauger, MA;Sancar, A
通讯作者：
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DOI：
10.1111/j.1365-2613.2006.00480.x
发表时间：
2006-06-01
影响因子：
3
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
3.4
作者：
Johnston, CJ;Williams, JP;Finkelstein, JN
通讯作者：
Finkelstein, JN