Protective effects of grape seed proanthocyanidins on cerebral ischemia-reperfusion injury in mice

Xiuxiang WU; Shuyun LI; Yuanyuan LIU

ABSTRACT

BACKGROUND:

Researches find that grape seed proanthocyanidins (GSP) can eliminate free radicals, protect heart against ischemia-reperfusion injury and enhance learning and memory abilities in experimental animal, but their effects on the cerebral ischemia-reperfusion injury remain unclear.

OBJECTIVE:

To study the protective effects of proanthocyanidins derived from grape seeds on the cerebral ischemic reperfused brain by measuring the total antioxidative capacity (T-AOC), nitric oxide synthase activities and malondialdehyde (MDA) content in brain tissue of mice.

DESIGN:

A completely randomized and controlled study.

SETTING:

Department of Pathophysiology and Functional Central Laboratory, Jinzhou Medical College; Department of Neurology, the First Affiliated Hospital of Jinzhou Medical College.MATERIALS The experiment was conducted in the Department of Functional Central Laboratory, Jinzhou Medical College from March to August 2004. Forty Kunming mice, provided by the Experimental Animal Center, Jinzhou Medical College, were randomly divided into five groups sham control group, cerebral ischemia-reperfusion group (IR group) and cerebral ischemia-reperfusion treated with low or high dose of GSP or nimdipine (IR+GSP or IR+Nim) group with eight mice in each group.

METHODS:

① Animal model establishment The animals were anesthetized with ether. Then they were incised through median incision of the neck. The bilateral common carotid arteries were then occluded by microaneurysm clips for 30 minutes. After removing the clips, return of flow was visualized in the arteries. ② Model group and control groupThe mice in low or high dose of GSP treated group or nimdipine treated group were injected GSP or nimdipine 10, 40, 2 mg/kg body mass respectively during the common carotid arteries occlusion and again at 24hours after reperfusion, while the mice in sham control group were injected the same volume distilled water with 40 mg/kg body mass. After 72-hour reperfusion, nitric oxide synthase activities, the total antioxidative capacity and MDA content in brain tissue of mice in each group were detected with chemical chromatometry. ③ The results were assessed by t test.MAIN OUTCOME

MEASURES:

Nitric oxide synthase activities, the total antioxidative capacity and MDA content in brain tissue of mice in each group were detected.

RESULTS:

Data of forty Kunming mice was entered the results analysis without any loss. ① Total antioxidative capacity Total antioxidative capacity in cerebral ischemia-reperfusion group was obvious lower than that in the sham control group (t=8.145, P=0.000) while total antioxidative capacity in low or high dose of GSP treated group and nimdipine treated group was obvious higher than that in the cerebral ischemia-reperfusion group (t=6.313, 8.956, 4.14, P ＜ 0.01). ② Nitric oxide synthase activities Nitric oxide synthase activities in cerebral ischemia-reperfusion group was obvious higherthan that in the sham control group (t=12.541, P ＜ 0.01), while nitric oxide synthase activities in low or high dose of GSP treated group and nimdipine treated group was obvious lower than that in the cerebral ischemia-reperfusion group (t=2.231, 8.956, 7.260, P ＜ 0.05-0.01). ③ MDA content MDA content in cerebral ischemia-reperfusion group was obvious higher than that in the sham control group (t=7.883, P ＜ 0.01), while high dose of GSP treated group and nimdipine treated group was obvious lower than that in the cerebral ischemia-reperfusion group (t =5.234,4.518, P ＜ 0.01).

CONCLUSION:

GSP exerted a protective effect on the cerebral ischemic reperfused brain by enhancing total antioxidative capacity and reducing lipid peroxidantion and nitric oxide synthase activities.