Effect of betulinic acid on spatial learning and memory in type 2 diabetic rats and its mechanism / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the effects of betulinic acid on spatial learning and memory in rats with type 2 diabetes mellitus(T2DM) and to explore its underlying mechanisms.Methods Forty-five male Wistar rats were randomly divided into control group (Sham),T2DM group and betulinic acid treatment group (BA) with 15 in each group.The rats in the latter two groups were given a high fat diet plus low dose of streptozotocin (STZ) to induce T2DM,and the rats in BA group was given 10 mg/kg BA for intragastric administration once daily for 12 weeks,the rats in T2DM group and Sham group were given an equal volume of physiological saline.Morris water maze method was used to detect the cognitive function.The mRNA levels of synaptic plasticity related protein GAP-43,SYP and PSD-95 were detected by RT-PCR.The protein expressions of cholinergic neurotransmitter ChAT and Ach were detected by Elisa.Results Compared with the Sham group,the escape latency of the T2DM group was significantly prolonged on days 2-4 ((62.28 ± 2.97)s vs (47.09±2.16)s;(48.52±3.09) s vs (26.18±2.21)s;(42.31±2.80)s vs (13.42±1.23)s),the original platform quadrant time was significantly reduced ((24.60±2.42) s vs (41.85 ± 1.98) s),GAP-43,SYP,ChAT and Ach levels were significantly lower,the differences were statistically significant (the t values were 16.37,22.34,39.78,20.42,116.01,91.35,71.84,21.88 and 21.11,respectively,all P＜ 0.05).Compared with T2DM group,the escape latency of BA group in 2-4 days were significantly shortened ((55.61±2.75)s vs (62.28±2.97)s;(31.35±2.63)s vs (48.52±3.09)s;(42.31±2.80)s vs (16.58± 1.37) s),the original platform quadrant time increased significantly ((37.58± 2.31) s vs (24.60±2.42) s),and GAP-43,SYP,PSD-95,ChAT and Ach levels were significantly higher,and the differences were statistically significant (the t values were 6.80,16.21,33.54,14.55,41.83,35.23,36.20,12.82 and 9.97,respectively,all P＜0.05).Conclusion Betulinic acid can improve the spatial learning and memory of type 2 diabetic rats,and increasing the expression of GAP-43,SYP,PSD-95,ChAT and Ach may be its potential mechanism.