Roles of ERK pathway and Panax notoginoside treatment in hypoxic hypercapnia pulmonary hypertension in rats |
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Authors: | ZHU A-nan WANG Yuan-yuan WANG Shu-jun JIN Ke-ke WANG Yang WANG Wan-tie |
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Institution: | 1. Department of Pathophysiology, Wenzhou Medical College, Wenzhou 325035, China;
2. Department of Internal Medicine, TCM Hospital of Yuyao, Yuyao 315400, China. |
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Abstract: | AIM: To investigate the roles of Panax notoginoside (PNS) and ERK1/2 signaling pathway in the pathological process of chronic hypoxic hypercapnia pulmonary hypertension in rats.METHODS: The animal model of chronic hypoxic hypercapnia pulmonary hypertension was set up in 72 male Sprague-Dawley rats and the animals were randomly divided into 6 groups: normal (N) group, hypoxic hypercapnia for 3-day (H3d) group, hypoxic hypercapnia for 1-week (H1w) group, hypoxic hypercapnia for 2-week (H2w) group, hypoxic hypercapnia for 4-week (H4w) group and PNS treatment (Hp) group.The rats in Hp group were injected with PNS (50 mg·kg-1·d-1, ip) before placing the animals into the hypoxic hypercapnia chamber.The rats in other groups were injected with normal saline (2 mL/kg, ip).The morphological changes of the pulmonary artery were observed under microscope with HE staining.Western blotting was used to detect the protein expression of p-ERK.The protein levels of p-ERK in the lung tissues and pulmonary blood vessels were determined by immunohistochemistry.RESULTS: The ratios of WA/TA in H1w, H2w, H4w and Hp groups were higher than that in N group (P<0.05).The ratio of WA/TA in Hp group was obviously lower than that in H4w group (P<0.05).The protein expression of p-ERK was barely positive in N group, but was up-regulated in the pulmonary tissues in all hypoxic rats.Compared with N group, the protein level of p-ERK was markedly up-regulated in H3d group, reached its peak in H2w group, and tended to decline in H4w group (P<0.05).In pulmonary arterial tunica intima and tunica media, p-ERK protein was dramatically expressed in all hypoxic rats compared with the control animals (P<0.05).In the lung tissues, the protein level of p-ERK in Hp group was lower than that in H4w group (P<0.05).In pulmonary arterial tunica intima and tunica media, the protein level of p-ERK in Hp group was lower by 84.86% than that in H4w group (P<0.05).CONCLUSION: ERK1/2 as a signal transducer may play an important role in the development of hypoxia and hypercapnia induced pulmonary hypertension.PNS inhibits the expression of ERK1/2, thus attenuating the development of pulmonary hypertension and improving pulmonary vascular remodeling. |
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Keywords: | Panax notogino side Hypoxia Hypercapnia Pulmonary artery ERK pathway |
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