Effect of tanshinone II A on MMP-2 and iNOS expression and free radical release in hippocampus of rat Alzheimer's disease model / 第二军医大学学报

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.