細(xì)胞系
C57BL/6小鼠腎內(nèi)皮細(xì)胞
溶解方法
在DMSO中的溶解度> 11.65 mg/mL。為了獲得更高濃度,可以將離心管在37℃加熱10分鐘和/或在超聲波浴中震蕩一段時(shí)間。原液可以在-20℃以下儲(chǔ)存幾個(gè)月。
反應(yīng)時(shí)間
應(yīng)用
經(jīng)4小時(shí)的TNF處理所造成的小鼠腎內(nèi)皮細(xì)胞凋亡能夠極大地被廣譜caspase抑制劑Boc-D-fmk所抑制,caspase-3 抑制劑 z-DQMD-fmk也能達(dá)到同樣的效果。此外,廣譜caspase抑制劑Boc-D-fmk也能顯著抑制TNF誘導(dǎo)的ICAM-1和VCAM-1mRNA的表達(dá)。
動(dòng)物模型
雄性SD大鼠
劑量
腹腔給藥1.5 mg/kg
注意事項(xiàng)
請(qǐng)測(cè)試所有化合物在室內(nèi)的溶解度,實(shí)際溶解度和理論值可能略有不同。這是由實(shí)驗(yàn)系統(tǒng)的誤差引起的,屬于正?,F(xiàn)象。
References:
[1.][1] Wu X, Guo R, Chen P, Wang Q, Cunningham PN. TNF induces caspase-dependent inflammation in renal endothelial cells through a Rho- and myosin light chain kinase-dependent mechanism. Am J Physiol Renal Physiol. 2009 Aug;297(2):F316-26. doi: 10.1152/ajprenal.00089.2009. Epub 2009 May 6.
[2.][2] Sheen-Chen SM, Hung KS, Eng HL. Effect of Boc-D-Fmk on hepatocyte apoptosis after bile duct ligation in rat and survival rate after endotoxin challenge. J Gastroenterol Hepatol. 2008 Aug;23(8 Pt 1):1276-9. doi: 10.1111/j.1440-1746.2008.05368.x. Epub 2008 Mar 27.
Boc-D-FMK是一種細(xì)胞通透性的廣譜caspase抑制劑,可完全抑制腫瘤壞死因子α的促凋亡效應(yīng),IC50值為39 μM[1]。
Boc-D-FMK可減弱核因子活化B細(xì)胞κ輕鏈增強(qiáng)子(NF-kB)的激活,抑制免疫球蛋白κ輕鏈基因增強(qiáng)子抑制蛋白α(IkBα)亞基的磷酸化作用,并抑制TNF誘導(dǎo)的細(xì)胞間粘附分子1(ICAM-1)和血管細(xì)胞黏著分子1(VCAM-1)的表達(dá)[2]。
此外,在膽總管結(jié)扎大鼠模型中, Boc-D-FMK可有效減少肝細(xì)胞凋亡,提高存活率[3]。
參考文獻(xiàn): [1] Cowburn AS, White JF, Deighton J, Walmsley SR, Chilvers ER.? z-VAD-fmk augmentation of TNF alpha-stimulated neutrophil apoptosis is compound specific and does not involve the generation of reactive oxygen species. Blood. 2005 Apr 1;105(7):2970-2. Epub 2004 Nov 30.[2] Wu X, Guo R, Chen P, Wang Q, Cunningham PN.? TNF induces caspase-dependent inflammation in renal endothelial cells through a Rho- and myosin light chain kinase-dependent mechanism. Am J Physiol Renal Physiol. 2009 Aug;297(2):F316-26. doi: 10.1152/ajprenal.00089.2009. Epub 2009 May 6.[3] Sheen-Chen SM, Hung KS, Eng HL.? Effect of Boc-D-Fmk on hepatocyte apoptosis after bile duct ligation in rat and survival rate after endotoxin challenge. J Gastroenterol Hepatol. 2008 Aug;23(8 Pt 1):1276-9. doi: 10.1111/j.1440-1746.2008.05368.x. Epub 2008 Mar 27.
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