Tin-mesoporphyrin,强大的血红素加氧酶抑制剂,用于治疗脑出血:体内和体外研究。

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瓦格纳KR、华Y de Courten-Myers通用,Broderick JP,西村RN, SY,德怀尔

Tin-mesoporphyrin,强大的血红素加氧酶抑制剂,用于治疗脑出血:体内和体外研究。

细胞杂志(Noisy-le-grand)。2000年5月,46 (3):597 - 608。

PubMed ID

10872746 (在PubMed

]

文摘

自发性脑出血(我)是中风亚型与死亡率和发病率最高。我也会发生创伤性脑损伤和溶栓后缺血性中风和心肌梗死。ICH-induced半球水肿的发展可以提高颅内压力,导致死亡。在幸存者中,edema-related白质损伤会导致终身神经赤字。目前,没有科学证明治疗我。血红素加氧酶产品,特别是铁和胆红素,可以对细胞毒性。在脑缺血模型中,金属是强有力的血红素加氧酶抑制剂,减少水肿和梗塞大小。Tin-mesoporphyrin (SnMP)是一个neuroprotectant,临床上也被用于治疗高胆红素血。目前,我们测试的假设SnMP治疗将减少水肿发展后实验我。我们生产血肿pentobarbital-anesthetized猪(9 - 11公斤)注入自体血到额叶白质。 To maximize tissue concentrations, SnMP (87.5 microM in DMSO) or DMSO (vehicle controls) was included in the infused blood. Pig brains were frozen in situ at 24 hrs. following ICH and hematoma and edema volumes were determined on coronal sections by computer-assisted image analysis. We also examined the effects of SnMP in vitro on ferritin iron release, the formation of iron-induced thiobarbituric acid reactive substances (TBARS) and initial clot formation and hemolysis. SnMP treatment significantly reduced intracerebral mass following ICH. This was due to significant decreases in hematoma (0.68+/-0.08 vs. 1.39+/-0.30 cc, vehicle controls p<0.025) and edema volumes (edema = 1. 16+/-0.33 vs. 1.77+/-0.31 cc, p<0.05). In vitro, SnMP did not stabilize ferritin iron against reductive release nor did it decrease iron-induced TBARS formation in brain homogenates. SnMP or DMSO added to pig blood did not alter clot weights. In conclusion, SnMP reduced intracerebral mass in an ICH model by decreasing both hematoma and edema volumes SnMP's mechanism of action is presently unknown but may involve its potent inhibition of heme oxygenase activity. SnMP's effect appears unrelated to ferritin iron release, antioxidant activity or initial clot formation. Since SnMP treatment could be brain protective following ICH, further investigations into neurological and neuropathological outcomes and as well as into its mechanism of action are warranted.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Stannsoporfin	血红素加氧酶1	蛋白质	人类	未知的	不可用	细节
Stannsoporfin	血红素加氧酶- 2	蛋白质	人类	未知的	不可用	细节