Hydrogen sulfide improves wound healing via restoration of endothelial progenitor cell functions and activation of angiopoietin-1 in type 2 diabetes.
Hydrogen sulfide improves wound healing via restoration of endothelial progenitor cell functions and activation of angiopoietin-1 in type 2 diabetes.
复制标题
硫化氢通过恢复内皮祖细胞功能和激活 2 型糖尿病患者的血管生成素-1 来改善伤口愈合
作者：
Liu F;Chen DD;Sun X;Xie HH;Yuan H;Jia W;Chen AF
血管生成障碍及其诱导的难治性伤口病变是糖尿病常见的并发症。据报道，硫化氢（H2S）具有促血管生成作用。我们假设硫化氢通过恢复2型糖尿病患者的内皮祖细胞（EPC）功能来改善糖尿病伤口愈合。db/db小鼠用硫氢化钠（NaHS）、4-羟基硫代苯甲酰胺（HTB）组或生理盐水处理18天。db/+小鼠用dl-炔丙基甘氨酸（PAG）或盐水处理18天。与糖尿病对照组相比，db/db小鼠血浆H2S水平显著降低，NaHS和HTB小鼠血浆H2S水平恢复。NaHS和HTB组的伤口闭合率显著快于db/db组，而PAG组的伤口闭合率较慢。NaHS和HTB组的伤口皮肤毛细血管密度增加。EPC功能在NaHS和HTB组中显著保留，但在PAG组中降低。同时，经PAG处理或CSE沉默后，db/+小鼠的EPC功能明显降低;经NaHS处理后，db/db小鼠的EPC功能明显改善。与db/db对照组相比，NaHS和HTB组伤口皮肤组织和EPCs中Ang-1的表达上调，但与正常对照组相比，体内PAG和体外siCSE处理下调。与仅用NaHS处理的db/db EPCs相比，NaHS处理前Ang-1小干扰RNA显著抑制糖尿病EPC管形成能力。总之，这些结果表明，H2S通过恢复2型糖尿病小鼠中的EPC功能和激活Ang-1来改善伤口愈合。
Impaired angiogenesis and its induced refractory wound lesions are common complications of diabetes. Hydrogen sulfide (H2S) has been reported to have proangiogenic effects. We hypothesize that H2S improves diabetic wound healing by restoring endothelial progenitor cell (EPC) function in type 2 diabetes. db/db Mice were treated with sodium hydrosulfide (NaHS), 4-hydro-xythiobenzamide group (HTB), or saline for 18 days. db/+ Mice were treated with dl-propargylglycine (PAG) or saline for 18 days. Plasma H2S levels were significantly decreased in db/db mice and restored in the NaHS and HTB mice compared with the diabetic control group. Wound-closure rates were significantly faster in the NaHS and HTB groups than in the db/db group, in which the PAG group had slower wound-closure rates. Wound skin capillary densities were enhanced in the NaHS and HTB groups. EPC functions were significantly preserved in the NaHS and HTB groups but were decreased in the PAG group. Meanwhile, EPC functions of the db/+ mice were significantly reduced after in vitro PAG treatment or cystathionine-γ-lyase (CSE) silencing; EPC functions of db/db mice were significantly improved after in vitro NaHS treatment. The expressions of Ang-1 in wound skin tissue and in EPCs were upregulated in the NaHS and HTB groups compared with db/db controls, but were downregulated by in vivo PAG and in vitro siCSE treatment compared with normal controls. Diabetic EPC tube formation capacity was significantly inhibited by Ang-1 small interfering RNA before NaHS treatment compared with db/db EPCs treated with NaHS only. Taken together, these results show that H2S improves wound healing by restoration of EPC functions and activation of Ang-1 in type 2 diabetic mice.
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影响因子：
2.2
作者：
Henderson, Peter W.;Singh, Sunil P.;Spector, Jason A.
通讯作者：
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影响因子：
1.8
作者：
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影响因子：
3.5
作者：
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影响因子：
16.2
作者：
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通讯作者：
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影响因子：
3.3
作者：
Fiorina, Paolo;Pietramaggiori, Giorgio;Orgill, Dennis P.
通讯作者：
Orgill, Dennis P.