Expression And Significance Of PCSK9 And LOX-1 In Hippocampus Of T2DM Rats

Objectives To investigate the expression of hippocampus proprotein convertase subtilisin/kexin type 9(PCSK9)and Lectin-like ox-LDL receptor-1(LOX-1)in type 2 diabetes mellitus(T2DM)rats and to explore its relationship with hippocampal injury in rats.Methods 19 male GK rats [13 weeks old,weighing(290±10)g] were selected as the model group(DM group),and the same age and weight of 17 Wistar rats were selected as the normal controls group(NC group),Fasting blood glucose(FBG),Fasting insulin(FINS),homeostasis model assessment-insulin resistance(HOMA-IR),total cholesterol(TC),Triglycerides(TG)and glycosylated hemoglobin(HbA1c)were measured in the second and 10 th weeks of feeding,using Morris water maze test to evaluate the learning and memory ability of rats,the rats were sacrificed in the 10 th week,the hippocampus was removed.Histopathological changes in CA1 region of hippocampus were observed by HE staining.Immunohistochemistry method was used to detect the expression of PCSK9 and LOX-1 protein in CA1 region of hippocampus of each group,and Western blot method was used to detect the expression of PCSK9,caspase-3,LOX-1 and Bcl-2 protein.Results 1.General conditions Rats in the control group had a steady increase in weight,good growth and development,active action,with a bright fur.the weight was similar in both groups after 2 weeks of feeding,and it was decreased significantly after 10 weeks of feeding.2.Biochemical index With the extension of time,FPG increased gradually in the model group,which were significantly higher than those in the control group,FINS,HOMA-IR,TC and were all higher in the model group than those in the control group in the 10 th week of feeding(P <0.05),weight was lower in the model group than those in the control group in the 10 th week of feeding(P <0.05).The difference between the two groups of TG was no statistical significance.3.Compared with the control group,the escape latency was significantly prolonged in the model group in the 10 th week of feeding(P <0.05),and the spatial probe test in the platform quadrant was significantly reduced(P <0.05).4.HE staining results in the 10 th week of feeding,hippocampus HE staining of two groups rats show that the hippocampal cells of the control group were neatly arranged,the structure is clear,the shape is regular,the hippocampal cells of the model group were sparsely arranged,the cytoplasm showed irregularities such as shrinkage and swelling,the shape of nucleus were irregular,some were lightly stained,showing nuclear pyknosis and vacuolation.5.The results of immunohistochemistry showed that The positive rates of PCSK9 and LOX-1immunereactive neurons in model group were more than those in the control group significantly(P <0.05).Western blot results showed that the expression of PCSK9,LOX-1 and caspase-3 in hippocampus of model group were significantly more than that of control group(P <0.05),the expression of Bcl-2 in hippocampus of model group was less than that of control group(P <0.05).Conclusions 1 Diabetic rats showed hyperglycemia,hyperlipidemia and insulin resistance,behavioral experiments show decreased cognitive function.2 Diabetic rats hippocampal CA1 cell were sparsely arranged,the cytoplasm showed irregularities such as shrinkage and swelling,the nucleus were irregular,showing nuclear pyknosis and vacuolation.3.The expression of PCSK9 and LOX-1 in hippocampus of diabetic rats increased significantly.