钙敏感受体通过JNK途径参与内毒素心肌损伤*

目的: 观察内毒素所致的心肌损伤中,钙敏感受体(CaSR)对c-Jun氨基末端激酶 (JNK)途径的影响。方法: 腹腔注射内毒素(5 mg/kg)制作新生大鼠内毒素心肌损伤模型,Wistar新生大鼠随机分为6组:对照组、内毒素组、CaSR激动剂组、CaSR抑制剂组、JNK抑制剂组、CaSR抑制剂+JNK抑制剂组。HE染色观察心肌形态, 测定血清乳酸脱氢酶(LDH)含量,PCR检测IL-6的mRNA表达,Western blot检测CaSR及JNK的蛋白表达。结果: 与对照组相比,内毒素组心肌损伤加重,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达均明显增加(P＜0.05)。与内毒素组比较,CaSR激动剂组心肌损伤加重,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达增加(P＜0.05); CaSR抑制剂组心肌损伤减轻,LDH含量、CaSR和JNK的蛋白表达减少(P＜0.05);JNK抑制剂组心肌损伤进一步减轻,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达均减少(P＜0.05);CaSR抑制剂+JNK抑制剂组心肌损伤明显减轻,LDH含量、IL-6的mRNA表达、CaSR和JNK的蛋白表达进一步减少(P＜0.05)。结论: CaSR可能通过JNK途径参与内毒素所致的心肌损伤。

Calcium-sensing receptor promotes endotoxin-induced myocardial injury through the JNK pathway

Objective: To investigate the effects of calcium-sensing receptor (CaSR) on the c-Jun N-terminal kinase (JNK) in myocardial injury induced by endotoxin. Methods: The endotoxic model of neonatal rats was made by intraperitoneal injection of LPS(5 mg/kg). Neonatal Wistar rats were randomly divided into 6 groups: ①control group (saline group), ②endotoxin (LPS) group, ③LPS + CaSR agonist group, ④LPS + CaSR inhibitor group, ⑤LPS + JNK inhibitor group, ⑥LPS + CaSR inhibitor + JNK inhibitor group. The morphology of myocardium was observed by HE staining. The content of lactate dehydrogenase(LDH) in serum was determined. And the expression of IL-6 mRNA was detected by PCR. The protein expressions of CaSR and JNK were analyzed by Western blot. Results: Compared with the control group, the myocardial injury was aggravated in the LPS group. The content of LDH and the expressions of IL-6 mRNA, CaSR and JNK were increased significantly (P＜0.05). Compared with the LPS group,myocardial injury was aggravated in the CaSR agonist group. The content of LDH and the expressions of IL-6 mRNA,CaSR and JNK were increased (P＜0.05). In the CaSR inhibitor group,myocardial injury was reduced. The content of LDH and the expressions of CaSR and JNK were decreased (P＜0.05). In the JNK inhibitor group,myocardial injury was further alleviated. The content of LDH and the expressions of IL-6 mRNA, CaSR and JNK were decreased (P＜0.05). Myocardial injury was significantly reduced in the CaSR inhibitor + JNK inhibitor group. The content of LDH and the expressions of IL-6 mRNA, CaSR and JNK were further reduced (P＜0.05). Conclusion: CaSR is involved in myocardial injury induced by LPS in neonatal rats perhaps through the JNK pathway.