Zhu A-Nan, Wang Shu-Jun, Wang Yuan-Yuan, Jin Ke-Ke, Wang Wan-Tie
Department of Pathophysiology , Wenzhou Medical College, Wenzhou 325053, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2012 Jan;28(1):79-83.
To investigate the role and significance of P38-MAPK in the pathological process of hypoxic hypercapnia pulmonary hypertension in rats, and the protection of panax notoginoside (PNS).
(1) To set up rat pathological model of hypoxic hypercapnia pulmonary hypertension: seventy two male SD rats (200 280 g) were randomly divided into six groups (n = 12), which were normal group (N group), hypoxic hypercapnia for 3-day group (H3d), hypoxic hypercapnia for 1-week group(H1w), hypoxic hypercapnia for 2-week group (H2w), hypoxic hypercapnia for 4-week group (H4w) and PNS-injected group (Hp). The rats of PNS -injected group were injected PNS before being placed in the chamber (50 mg/(kg x d), ip), and other groups were injected normal sodium (2 ml/kg, ip). (2) The shapes of pulmonary artery were detected by HE staining. (3) Western blot was used to study the protein expression of p38-MAPK. The expression of p38-MAPK in lung tissue and pulmonary blood vessel was investigated by immunohistochemistry.
(1) The ratio of vessel wall area/total area (WA/ TA) in H1w, H2w, H4w and Hp group was higher than that of N group (P < 0.05), but that of H3d group did not change obviously (P > 0. 05 vs N group). The ratio of WA/TA in Hp group was obviously lower than that of H4w, group (P < 0.05). (2) The levels of P-p38 protein was markedly ascended in H3d group (0.225 +/- 0.071) compared with N group (0.012 +/- 0.006), and expression of P-p38 protein was significantly positive in H1w, H2w, H4w groups. (P < 0.05). (3) As P-p38 protein in pulmonary arterial tunica intima and tunica media, sterile expression in N group (0.099 +/- 0.015) and H3d group (0.107 +/- 0.013) contrasted to H4w group (0.124 +/- 0.025, P < 0.05), then tended to rise in H2w, H4w group (P < 0.05). (4) In pulmonary tissue, the levels of P-p38 protein in PNS-injected group were lower 53.02% (P < 0.05) than those in H4w group. In pulmonary arterial tunica intima and tunica media the levels of P-p38 protein in PNS-injected group were lower 87.33% (P < 0.05) than those in H4w group.
p38-MAPK as a signal transduction 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 related to its inhibiting expression of p38 MAPK.
探讨P38丝裂原活化蛋白激酶（P38-MAPK）在大鼠低氧高碳酸血症性肺动脉高压病理过程中的作用及意义，以及三七总皂苷（PNS）的保护作用。
（1）建立大鼠低氧高碳酸血症性肺动脉高压病理模型：72只雄性SD大鼠（200～280g）随机分为6组（n = 12），即正常组（N组）、低氧高碳酸血症3天组（H3d）、低氧高碳酸血症1周组（H1w）、低氧高碳酸血症2周组（H2w）、低氧高碳酸血症4周组（H4w）和PNS注射组（Hp）。PNS注射组大鼠在放入氧舱前腹腔注射PNS（50mg/(kg·d)），其他组腹腔注射生理盐水（2ml/kg）。（2）采用苏木精-伊红（HE）染色检测肺动脉形态。（3）用蛋白质免疫印迹法研究p38-MAPK蛋白表达。采用免疫组织化学法检测肺组织和肺血管中p38-MAPK的表达。
（1）H1w、H2w、H4w和Hp组的血管壁面积/总面积（WA/TA）比值高于N组（P < 0.05），但H3d组无明显变化（与N组比较，P > 0.05）。Hp组的WA/TA比值明显低于H4w组（P < 0.05）。（2）与N组（0.012±0.006）比较，H3d组P-p38蛋白水平显著升高（0.225±0.071），H1w、H2w、H4w组P-p38蛋白表达显著阳性（P < 0.05）。（3）肺动脉内膜和中膜中P-p38蛋白，N组（0.099±0.015）和H3d组（0.107±0.013）的表达与H4w组（0.124±0.025，P < ；0.05）相比有差异，然后在H2w、H4w组中呈上升趋势（P < 0.05）。（4）在肺组织中，PNS注射组的P-p38蛋白水平比H4w组低53.02%（P < 0.05）。在肺动脉内膜和中膜中，PNS注射组的P-p38蛋白水平比H4w组低87.33%（P < 0.05）。
p38-MAPK作为一种信号转导分子可能在低氧诱导的肺动脉高压发展中起重要作用。PNS降低肺动脉高压和改善肺血管壁重塑的作用可能与其抑制p38 MAPK的表达有关。
