Atrial remodeling in diabetes is partially attributed to NF-κB/TGF-β signal transduction pathway activation. We examined whether the hyperglycemia-induced increased expression of NF-κB/TGF-β was dependent upon protein kinase C-β (PKCβ) and tested the hypothesis that selective inhibition of PKCβ using ruboxistaurin (RBX) can reduce NF-κB/TGF-β expression and inhibit abnormal atrial remodeling in streptozotocin (STZ)–induced diabetic rats. The effects of PKCβ inhibition on NF-κB/TGF-β signal transduction pathway-mediated atrial remodeling were investigated in STZ-induced diabetic rats. Mouse atrial cardiomyocytes (HL-1 cells) were cultured in low- or high-glucose or mannitol conditions in the presence or absence of small interference RNA that targeted PKCβ. PKCβ inhibition using ruboxistaurin (RBX, 1 mg/kg/day) decreased the expression of NF-κBp65, p-IκB, P38MARK, TNF-α, TGF-β, Cav1.2, and NCX proteins and inducibility of atrial fibrillation (AF) in STZ-induced diabetic rats. Exposure of cardiomyocytes to high-glucose condition activated PKCβ and increased NF-κB/TGF-β expression. Suppression of PKCβ expression by small interference RNA decreased high-glucose–induced NF-κB and extracellular signal–related kinase activation in HL-1 cells. Pharmacological inhibition of PKCβ is an effective method to reduce AF incidence in diabetic rat models by preventing NF-κB/TGF-β-mediated atrial remodeling.

糖尿病的心房重构部分归因于NF-κB/TGF-β信号转导途径的激活。我们检查了高血糖诱导的NF-κB/TGF-β表达增加是否依赖于蛋白激酶C-β（PKCβ），并检验了使用ruboxistaurin（RBX）选择性抑制PKCβ可以降低NF-κB/TGF-β的假设。 β表达并抑制链脲佐菌素（STZ）诱导的糖尿病大鼠的心房重构异常。在STZ诱导的糖尿病大鼠中研究了PKCβ抑制作用对NF-κB/TGF-β信号转导途径介导的心房重构的影响。在存在或不存在靶向PKCβ的小干扰RNA的情况下，在低或高葡萄糖或甘露醇条件下培养小鼠心房心肌细胞（HL-1细胞）。使用卢布司他林（RBX，1 mg / kg /天）抑制PKCβ会降低NF-κBp65的表达，STZ诱导的糖尿病大鼠中p-IκB，P38MARK，TNF-α，TGF-β，Cav1.2和NCX蛋白与房颤（AF）的诱导性。心肌细胞暴露于高葡萄糖状态会激活PKCβ，并增加NF-κB/TGF-β的表达。小干扰RNA抑制PKCβ的表达降低了HL-1细胞中高糖诱导的NF-κB和细胞外信号相关激酶的活化。PKCβ的药理抑制是通过预防NF-κB/TGF-β介导的心房重构来降低糖尿病大鼠模型中AF发生的有效方法。小干扰RNA抑制PKCβ的表达降低了HL-1细胞中高糖诱导的NF-κB和细胞外信号相关激酶的活化。PKCβ的药理抑制是通过预防NF-κB/TGF-β介导的心房重构来降低糖尿病大鼠模型中AF发生的有效方法。小干扰RNA抑制PKCβ的表达降低了HL-1细胞中高糖诱导的NF-κB和细胞外信号相关激酶的活化。PKCβ的药理抑制是通过预防NF-κB/TGF-β介导的心房重构来降低糖尿病大鼠模型中AF发生的有效方法。