| Objective:Preparing rats model of Alzheimer’s disease in order to observe the effect of tanshinone Ⅱ A on learning skills and memory capacity, plasma endotoxin, microglial cells and the expression of the related inflammatory factors of AD rats. To explore the possible protective mechanism of tanshinone ⅡA on AD in order to provide a new idea and direction for the effective treatment of AD.Methods:SD rats, quality were between 170 g to 220 g, male, and were divided into AD group,TSⅡA group and control group randomly, a total of three groups(n=12). The AD model was prepared by Aβ1-42 stereotactic injection into lateral cerebral ventricle, and the drug intervention was carried out by intraperitoneal injection of tanshinone Ⅱ A sodium sulfonate. Though performing morris water maze test, rat behavioral tests to detect the influence of tanshinone ⅡA on learning skills and memory capacity. Exploring the effects of tanshinone Ⅱ A on microglia and the expression of plasma LPS and the related inflammatory active molecules such as IL-1β, TNF-α though using immunohistochemistry and ELISA method.Results:1. Rats water maze behavioral tests: the results illustrated that comparing with the rats in control group, the escape response latency of AD rats significantly lengthen(P<0.05), Compared with the AD rats, the escape response latency of TSⅡA group wassignificantly decreased(P<0.05).2. ELISA for the detection of LPS and IL-1β, TNF-α: The effects displayed that the plasma endotoxin(LPS) level of AD model group was significantly higher than that of control group(P<0.05). The plasma LPS level of TSⅡA group was declined compared with the plasma LPS level of AD group(P<0.05). In AD group, the levels of IL-1β and TNF-α in plasma and brain tissue were higher than control group(P<0.05). And plasma and brain tissue’s levels of IL-1β and TNF-α in TSⅡA group were lower than that in AD group.3. Immunohistochemistry for the detection of Iba-1 positive cells: The results signified that Iba-1 positive cells(microglia) in cortex of AD group had large volume with the neurite retracted, and the quantity increased noticeably than the quantity of rats in control group(P<0.05). The microglia in cerebral cortex of TS II A group became less than AD model group, and the quantity was evidently reduced(P<0.05).Conclusions:1. The AD model was created by Aβ1-42 stereotactic injection into lateral cerebral ventricle, water maze behavioral test consequences signified that the learning skills and memory capacity of AD rats declined, indicating that the AD rat model is successful replication.2. The levels of plasma LPS and inflammatory active molecules such as IL-1β and TNF-α in plasma of AD group increased, which signified that the rats in AD group had intestinal endotoxemia(IETM).3. After tanshinone ⅡA intraperitoneal injection, the learning and memory function of TS II A group was obviously alleviated, and indicating that tanshinone Ⅱ A could enhance the learning skills and memory capacity of AD rats.4. Compared with the AD group, the levels of LPS, IL-1β and TNF-α in plasma of TS II A group declined, the number of microglia in brain and the levels of IL-1β and TNF-αproduced by MG both reduced, which indicated that tanshinone ⅡA probably reduced inflammatory response in AD rats with IETM via decreasing the level of LPS, inhibitingthe hyperplasia of microglia, and further weakening the expression of inflammatory active molecules such as IL-1β and TNF-α, accordingly playing a protective role against AD. |
