Effect of tanshinone Ⅱ A on MMP-2 and iNOS expression and free radical release in hippocampus of rat Alzheimer's disease model

Abstract

Objective To investigate the influence of tanshinone Ⅱ A on learning and memory ability,expression of inducible nitric oxide synthase(iNOS),matrix metalloproteinase Ⅱ(MMP-2) and release of free radicals in the hippocampus of rat Alzheimer' s disease(AD) model,and to explore the related mechanism.Methods Rat AD models were established by direct β-amyloid protein(Aβ) injection method.For tanshinone Ⅱ A(Tan Ⅱ A) intervention test,the learning and memory ability of the AD rats were observed,the expressions of iNOS,MMP-2 at gene and protein levels were determined and their correlation were analyzed,and the release of free radical in the hippocampus region of AD rats was quantified.Results The expressions of iNOS and MMP-2 in the hippocampus region of AD rats were significantly higher than that in the control group(P 0.05),and the expressions of iNOS and MMP-2 were positively correlated at both mRNA and protein levels(P 0.05).Meanwhile,nitric oxide(NO),ONOO-and reactive oxygen species(ROS) release in the hippocampus of AD rats were significantly higher than those in the control rats(P 0.05).The learning and memory ability was obviously decreased in AD model rats.Tan Ⅱ A intervention(50 mg/kg) significantly reduced the AD-induced release of NO,ONOO-,and ROS,and expression of iNOS(P 0.05) and MMP-2 protein(P 0.01) in the hippocampus region;it also greatly improved the learning and memory ability of AD model rats.Conclusion Tan Ⅱ A can effectively alleviated the AD symptoms,possibly by inhibiting AD-induced iNOS and MMP-2 expressions,reducing toxic free radical,and suppressing oxidative injury in AD rats.