Expression and significance of proprotein convertase subtilisin/kexin type 9 in hippocampus of type 2 diabetic rats

Abstract

Objective To investigate the expression of hippocampus proprotein convertase subtilisin/kexin type 9 (PCSK9) in type 2 diabetes mellitus (T2DM) rats and to explore its relationship with hippocampal injury in rats. Methods Nineteen healthy male Goto-Kakizaki (GK) rats were selected as model group [13 weeks old and (290±10)g] and seventeen healthy male wistar rats with the same age and genetic homology as model group were selected as control group [weight (290±10) g]. Weight, fasting blood glucose (FPG), glycosylated hemoglobinA1c (HbA1c) were measured after 2 and 10 weeks of feeding. Fasting C-Peptide (FCP), total cholesterol (TC) , triglycerides (TG), homeostasis model assessment-insulin resistance (HOMA-IR) were measured after 10 weeks of feeding. Using Morris water maze test to evaluate the learning and memory ability of rats after 10 weeks of feeding. Histopathological changes of hippocampus were observed by HE staining. Immunohistochemistry method was used to detect and analyze the expression levels of PCSK9 protein in hippocampus of each group, and Western blot method was used to detect and analyze the expression levels of PCSK9, cysteinyl aspartate specific proteinase caspase-3 (caspase-3) and B-cell lymphoma-2 (Bcl-2) protein. Using t test to compare the two groups. Results FPG, HbA1c, HOMA-IR and TC were all higher in the model group than those in the control group after 2 and 10 weeks of feeding (t=-29.305-7.813, P 0.05) . Morris water maze showed that compared with the control group, the escape latency of the model group rats was significantly prolonged in the navigation experiment after 10 weeks, and the quadrant residence time of the platform was significantly shortened in the space exploration experiment in the model group [ (24.2±3.7) vs (17.8±3.3) s, t=6.599, P<0.05]. The results of immunohistochemistry showed that the positive rates of PCSK9 immune-reactive neurons in model group increased than those in the control group significantly. Western blot results showed that the expression of PCSK9 and caspase-3 in hippocampus of model group increased significantly than that of control group (0.517±0.103 vs 0.806±0.114, 0.021±0.004 vs 0.136±0.019, t=-11.038, -19.598, both P<0.05) , the expression of Bcl-2 in hippocampus of model group was less than that of control group (t=8.099, P<0.05) . Conclusion The expression of PCSK9 increases in hippocampus of T2DM rats, which may be involved in the process of hippocampus injury in T2DM rats. Key words: Diabetes mellitus, type 2; Hippocampus; Proprotein convertase subtilisin/kexin type 9