| Background and ObjectiveCerebrovascular disease due to high morbidity and disability fatality rate to thesociety, family and individual caused serious economic and spirit burden, and affectthe quality of people’s lives, serious harm to human life and health. Therefore, to finddrug and method of the effective treatment and prevention of cerebrovascular diseaseand reduce ischemic brain injury became the focus of the medical research direction.There are no effective treatment methods to the ischemic cerebrovascular diseaseat present. Clinical early thrombolysis treatment is used, but at the same time it cancause more serious cerebral ischemia-reperfusion injury.Some research found thatafter cerebral ischemia some patients`blood vessels can recover recanalization afterthrombolysis treatment or natural recanalization, but after blood supply, which canlead to the brain tissue damage of the blood restored and nerve dysfunction isaggravating in some cases, namely the cerebral ischemia-reperfusion injury. The mainreason is the change of blood brain barrier (BBB) permeability, resulting in bleedingin the brain tissue edema and secondary injury. Research shows that the blood-brainbarrier integrityhas an important role in the process of cerebral ischemia reperfusioninjury.Blood brain barrier including blood-brain and blood-cerebrospinal fluid barrier, is a peculiar characteristic structure of brain capillaries, maintain stable of the body ofthe central nervous system internal environment, the change of the structure has greateffect on the central nervous system. Vascular basement membrane is composed ofthe extracellular matrix molecules, plays an important role in maintaining theintegrity of the blood-brain barrier, and extracellular matrix molecules is the maineffect of matrix metalloproteinases substrates. Research shows that both at home andabroad, matrix metalloproteinases2and matrix metalloproteinases9and degradationof extracellular matrix, destruction of blood-brain barrier.Resolvins is a kind of endogenous anti-inflammatory and Inflammation-Resolutionlipid medium derived from omega-3fatty acids including eicosapentaenoic acid (EPA)and docosahexaenoic acid (DHA). Resolvin D1is bio-synthesized from DHA.Studies show that intravenous injection DHA or a diet rich in DHA and EPA couldreduce nerve function damage induced by hypoxia or ischemia in rats. Studies havefound that omega-3polyunsaturated fatty acid can increase the angiogenesis aftercerebral ischemia, and provide long-term brain protection. Study found that RvD1hasprotective effect to ischemia reperfusion injury of liver, kidney, lung and other organs.And there has not been reported at home and abroad to the influence on cerebralischemia-reperfusion injury.This experiment adopts the ischemia-reperfusion injury model rats. To discuss theeffect of Resolvin D1to focal cerebral ischemia-reperfusion injury in rats, and thechange of the permeability of blood brain barrier, and to explore the possiblemechanism.Materials and MethodsGroupsChoose clean health adult male Sprague wrote Dawley rats (260-280g), all ratscompletely and randomly will be divided into five groups: The control+alcohol salinegroup:Sham; The cerebral ischemia reperfusion+alcohol saline group:I/R; cerebralischemia reperfusion+RvD1small-dose treatment group:RvD1(S); The cerebralischemia reperfusion+RvD1medium-dose treatment groups:RvD1(M); Cerebral ischemia reperfusion+RvD1large-dose treatment group:RvD1(L).Methods1. Through improved line plug method, Establishment and evaluation of reproductionof middle cerebral artery occlusion to produce cerebral ischemia with nylon thread inrat. Using10%chloral hydrate (350mg/kg) by intraperitoneal injection to anesthesia,line switch enter into from the common carotid artery via internal carotid artery, andafter2h anchored line pull out, the formation of cerebral ischemia reperfusion. After24h cerebral ischemia reperfusion, nerve function injury in rats with scores;2. Four azole nitrogen three benzene chloride (TTC) staining method for calculatingthe infarction volume changes in rats;3. Dry and wet ratio method to determine the water content of brain tissue;4. Ultraviolet spectrophotometer method to detect rats blood brain barrier (blood-brain barrier, BBB) of Evans blue (Evans blue, EB) the change of permeability;5. Western Blot method to detect matrix metalloproteinase-2(MMP-2) and matrixmetalloproteinase9(MMP-9) expression.Results1. All of the experimental group rats are awake after2h of anesthesia. Ischemiareperfusion for24h, evaluations showed that the clinical nerve function defects wereimproved (P<0.05). Sham group rats nerve function defect score of0, I/R group andRvD1group rats after anesthesia awake all have varying degrees of nerve functiondefect symptoms. Cerebral ischemia reperfusion for24h, compared withand I/Rgroup, RvD1(S) rat of the neural function defect scale did not significantly decreased(P>0.05), RvD1(M) group and RvD1(L) group decreased (P <0.05); compared withRvD1(L), RvD1(M) group of nerve function defect score lower (P <0.05).2. After TTC staining, the normal brain tissue is red, and the brain infarction is pale.Cerebral infarction volume of Sham group is0; And compared with I/R group, thecerebral infarction volume of RvD1(M) group and RvD1(L) group reduced (P <0.05); Compared with RvD1(L) group, cerebral infarction volume RvD1(M) groupdecreased (P <0.05). 3. Compared with the Sham group, the brain water content of the I/R group wasincreased (P <0.05); Compared with I/R group, the brain water content of the RvD1(M) group and RvD1(L) decreased (P <0.05);4. Compared with I/R group, EB content of the RvD1group (M) and RvD1(L) groupin brain tissue decreased (P <0.05); Compared with RvD1(L) group, RvD1(M)group reduced (P <0.05).5. The expression of MMP-2and MMP-9in Sham group is very low; I/R group andRvD1MMP-2and MMP–9increased (P <0.05); Compared with I/R group, RvD1(L) group and RvD1(M) group decreased (P <0.05); Compared with RvD1(L)group, RvD1(M) group were decreased (P <0.05).ConclusionResolvin D1can reduce rats nerve dysfunction after ischemia reperfusion injury,reduce the degree of cerebral infarction, to protect the integrity of the blood-brainbarrier, alleviate the degree of brain edema, its mechanism may be related to inhibitthe expression of MMP-2and MMP-9. |
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