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| Role of panax notoginoside in rats with hypoxic hypercapnia pulmonary hypertension induced by JNK signal transduction pathway |
| ZHOU Xiaoxiong YE Taochun LUO Chuanjin WU Hui CHU Qingmin ZHAO Xinjun |
| Department of Cardiology, the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangdong Province, Guangzhou 510504, China |
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Abstract Objective To investigate the dynamic change of JNK signaling pathway in the occurrence and development of hypoxic hypercapnia pulmonary hypertension in rats, discuss the mechanism of panax notoginoside (PNS) in the protection of hypoxic hypercapnia pulmonary hypertension. Methods Rats pathological models of hypoxic hypercapnia pulmonary hypertension were established: SD rats were randomly divided into three groups (n=10): normal group (N group), hypoxic hypercapnia for 4 week group (H4w group), and PNS-injected group (Hp4w group). RT-qPCR and Western blot were used to detect the expression of JNK. Primary cultured PASMCs, isolated from SD rats, were incubated in logarithmic growth phase from the 2nd to 5th generation. PASMCs were divided into five groups: normal group (N group), hypoxic hypercapnia group (H group), and R1 treated group with different concentrations (10, 50 and 100 mg/L) of notoginsenoside monomer R1 under the condition of 6% CO2 plus 1% O2 for 24 h (R10, R50 and R100 groups). The expressions of JNK mRNA and protein levels were detected by RT-qPCR and Western blot. PASMCs were treated with R1 and JNK inhibitor SP600125 for 5 days, CCK8 was used to detect the proliferation of PASMCs. Results ①The mPAP in H4w and Hp4w group was higher than that of N group (P < 0.05), but mPAP in Hp4w group was obviously lower than that of H4w group (P < 0.05). ②The mRNA and protein levels of JNK were significantly increased in H4w and Hp4w groups, compared with N group (P < 0.05), and Hp4w group was lower than H4w group (P < 0.05). ③The protein and mRNA expression levels of JNK in PASMCs were significantly higher in H group than those in N group (P < 0.05); compared with H group, in R1 treatment (10, 50 and 100 mg/L) groups, the expression levels of JNK were markedly decreased (P < 0.05). ④The proliferation of PASMCs were significantly inhibited in groups treated with R1 and JNK inhibitor SP600125 (P < 0.05). Conclusion JNK may play an important role in the development of hypoxia induced pulmonary hypertension. The effect of PNS on reducing pulmonary hypertension and improving pulmonary vascular wall remodeling may be partly related to its inhibition of JNK pathway.
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