Cerebral Injury And Acute Lung Injury Induced By Focal Cerebral Ischemia-reperfusion And Anti-injury Effects Of Zileuton

Objective To investigate pathological changes of the brain and the lung and to discussion the mechanisms of injury caused by focal cerebral ischemia–reperfusion injury (CIRI) in rats. To observe the protective effects and analysis the protective mechanisms of zileuton on the brain and lungs, which is a 5-lipoxygenase inhibitor.Methods The right middle cerebral artery in rats were occluded by inserting a thread through internal carotid artery for 2h, and then reperfused for 24h. Zileuton(10,50 mg·kg^-1) was orally administered 2h before ischemia and 0,5,10 h after reperfusion. The content of LTB₄ in serum was measured by enzyme linked immunosorbent assay (ELISA) technique; The mRNA of CysLTR₁ was detected by RT-PCR; The expressions of iNOS and TNF-αproteins were measured by immunohistochemical technique; The activities of MPO, T-AOC, GSH and Na⁺-K⁺-ATPase of the tissues from the brain and the lung were measured by biochemical method; Morphological changes of the lung tissue were observed by HE staining technique. Lung wet/dry weight ratios detected was to observe the water content of the lung.Results (1) After middle cerebral artery occlussion 2h/reperfusion 24h, the content of LTB₄ was elevated in serum; In the brain and lung tissues,the expression of CysLTR₁ mRNA was enhanced;The expressions of iNOS and TNF-αproteins were increased.The activity of MPO was increased and the activities of T-AOC, GSH and Na⁺-K⁺-ATPase were decreased; The pathological changes were appeared in the lung tissue. The wet/dry weight was significantly increased in the lung tissue.(2)Zileuton 10,50mg·kg^-1 can dramatically reduce the content of LTB₄ in serum, inhibit the expressions of CysLTR₁ mRNA and iNOS proteins in the brain and lung tissues,increase the activities of T-AOC in the brain tissue and Na⁺-K⁺-ATPase in the lung tissue, (3)Zileuton 10,50mg·kg^-1 can inhibit the expression of TNF-αprotein, reduce the activity of MPO, increase the activity of GSH; and increase the activities of T-AOC in the lung tissue and Na⁺-K⁺-ATPase in the brain tissue; alleviate the pathological changes in the lung;and reduce the wet/dry weight in the lung tissue; All of these zileuton 50mg·kg^-1 is even more prominence.Conclusion (1) CIRI can induce the injuries of the brain and lung tissues. CIRI cause the evident inflammatory reaction, oxidative damage and ionic transport disorder in the lung tissue.(2) Zileuton 10,50mg·kg^-1 can dramatically inhibit the expression of CysLTR₁mRNA and reduce the content of LTB₄ in serum after CIRI and play a protective roles in the brain and lung injuries. There are mechanisms may be as followings:zileuton can inhibit the activity of 5-lipoxygenase,inhibit the inflammation reaction and lipid peroxidation; inhibit the expression of iNOS protein and protect the activity of Na⁺-K⁺-ATPase.