Effect of pranlukast on memory impairment and nerve injury in streptozocin-induced type 1 diabetic mice / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the effect of pranlukast(Pran) on learning and memory impairment and neuroinflammatory and apoptotic response in streptozocin(STZ)-induced type 1 diabetic mice. METHODS Male ICR mice were injected through the tail vein with STZ(150 mg·kg-1)to induce the type 1 diabetes model. Diabetic mice were administered orally with Pran. After 4 consecutive weeks of administration,the escape latency in hidden platform trials,number of platform crossings and time spent in the target quadrant of mice were assessed by the Morris water maze(MWM)test. Western blot was used to detect the proteins of cysteinyl-leukotrienes receptor-1(CysLT1R)and pro-inflammatory factors,nuclear factor-κB p65 subunit(NF-κB p65),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and cleaved caspase 3,Bax and Bcl-2 in the hippocampus and prefrontal cortex of diabetic mice. We also determined fasting blood glucose,serum insulin and lipids such as triglyceride,total cholesterol,high density lipoprotein cholesterol,and low density lipoprotein cholesterol. RESULTS The data of the MWM test showed that untreated diabetic mice displayed a higher escape latency in hidden platform trials(P<0.05),and a smaller number of platform crossings(P<0.05)as well as shorter per?centage of time spent in the target quadrant(P<0.05). The data of Western blotting showed that treat?ment with Pran 0.6 and 1.2 mg·kg-1 significantly reduced the levels of CysLT1R,nuclear NF-κB p65, IL-1βand TNF-α,cleaved caspase 3,and the ratio of Bax and Bcl-2 in the hippocampus and prefrontal cortex of diabetic mice(P<0.05). However,Pran did not improve the fasting blood glucose,serum insulin or lipid metabolism disorder in diabetic mice. CONCLUSION Pran improves memory impairment and nerve injury in STZ-induced type 1 diabetic mice.