关键词: 失血性休克, 双氢青蒿素, Toll样受体4, 髓样分化因子88

Abstract: Objective To study the protective effect of dihydroartemisinin (DHA) on lung injury in rats with hemorrhagic shock (HS). Methods The rats were divided into sham operation group, model group (the left common carotid artery was treated by blood-letting, the blood volume was about 35% of the blood volume, the average arterial pressure dropped to 35~45 mmHg, and the Ringer's solution was resuscitated with twice the blood volume), DHA low- and high-dose groups (6 and 12 mg/kg DHA per day), dexamethasone group (10 mg/kg dexamethasone per day). Intervene was carried out continuously for 7 days. The wet weight/dry weight ratio(W/D) of the lung was measured.ELISA was used to determine the activity of myeloperoxidase (MPO), the level of IL-12, IL-1β and TNF-α in lung tissue. Hydroxylamine method was used to determine the activity of superoxide dismutase (SOD). The thiobarbituric acid colorimetric method was used to determine the malondialdehyde (MDA) level. HE staining was used to observe lung tissue pathology. Western blot was used to detect the relative expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB) p65, and p-NF-κB p65 protein in lung tissue. Results Compared with the sham operation group, the lung W/D, MDA, IL-12, IL-1β, and TNF-α levels, MPO activity, relative expression of TLR4, MyD88 protein, p-NF-κB p65/NF -κB p65 were all significantly increased in the model group, but SOD activity was significantly decreased(P＜0.05). Compared with the model group, lung W/D, lung tissue MDA, IL-12, IL-1β, and TNF-α levels, MPO activity, relative expression of TLR4, MyD88 protein, p-NF-κB p65/NF -κB p65 were significantly reduced in the low-dose and high-dose groups of DHA and the dexamethasone group, of which the SOD activity was significantly enhanced (P＜0.05). The model group was infiltrated with a large number of inflammatory cells, the pulmonary interstitial edema was obvious, and the number of alveoli was significantly reduced. The above-mentioned pathological changes improved after intervention in DHA low- and high-dose groups and dexamethasone group. Conclusions DHA reduces pathological changes, edema, oxidative damage and inflammation of lung tissue after HS, inhibits the expression of TLR4, MyD88 and NF-κB phosphorylation, and shows a protective effect on lung injury.

Key words: hemorrhagic shock, dihydroartemisinin, Toll-like receptor 4, myeloid differentiation factor 88