Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Clin Exp Pharmacol Physiol. 2012 Feb;39(2):136-40. doi: 10.1111/j.1440-1681.2011.05645.x.
The aims of the present study were to explore the effects of: (i) scutellarin (Scu) on protein kinase C (PKC) translocation caused by diabetic conditions in diabetic rat thoracic aorta; and (ii) phorbol-12-myristate-13-acetate (PMA) treatment of cultured thoracic aortic smooth muscle cells. Diabetes was induced in rats by streptozotocin and diabetic rats were divided into two groups: (i) an Scu-treated group, administered 0.1 g/kg Scu by gavage; and (ii) an aminoquanidine (AG)-treated group, which received dietary supplementation of 0.1% AG from Week 1 of diabetes induction. After 10 weeks, rats were killed and thoracic aortic smooth muscle cells were isolated and cultured. Cell fractions were obtained by ultracentrifugation and PKC activity was assayed by ELISA, whereas the distribution of PKC was verified by western immunoblotting. The PKC activity in the membrane fraction of thoracic aortic smooth muscle cells was significantly increased in diabetic compared with control rats, whereas the administration of Scu significantly inhibited this increase. Phorbol myristate acetate (100 nmol/L, 10 min) induced the translocation of the PKCα, βI, βII, δ and ε isoforms, whereas 48 h pretreatment of cells with 1 μmol/L Scu significantly inhibited PMA-induced PKCβI, βII and δ translocation. The results of the present study suggest that Scu inhibits the translocation of PKC in vivo and in vitro and may have value as a drug in the treatment of diabetic complications via its inhibition of PKC βI, βII and δ translocation.
（i）野黄芩苷（Scu）对糖尿病大鼠胸主动脉蛋白激酶 C（PKC）移位的影响；和（ii）佛波醇-12-肉豆蔻酸-13-醋酸酯（PMA）对培养的胸主动脉平滑肌细胞的作用。链脲佐菌素诱导大鼠糖尿病，将糖尿病大鼠分为两组：（i）Scu 治疗组，灌胃给予 0.1 g/kg Scu；和（ii）氨基胍（AG）治疗组，从糖尿病诱导的第 1 周开始给予饮食补充 0.1%AG。10 周后，处死大鼠并分离培养胸主动脉平滑肌细胞。通过超速离心获得细胞级分，并通过 ELISA 测定 PKC 活性，Western 免疫印迹验证 PKC 的分布。与对照组大鼠相比，糖尿病大鼠胸主动脉平滑肌细胞膜部分的 PKC 活性显著增加，而 Scu 的给予显著抑制了这种增加。佛波醇肉豆蔻酸酯（100nmol/L，10min）诱导 PKCα、βI、βII、δ和ε同工型的易位，而用 1μmol/L Scu 预处理细胞 48h 可显著抑制 PMA 诱导的 PKCβI、βII 和δ易位。本研究结果表明，Scu 抑制体内和体外 PKC 的易位，并且可能通过抑制 PKCβI、βII 和δ易位而具有作为治疗糖尿病并发症的药物的价值。
