Effects Of Hyperlipidemia On Cell Apoptosis And Expression Of PCSK9in Brain Tissue Of New Zealand Rabbits

Hyperlipidemia is an important risk factor for neurodegenerative diseases,neuronal apoptosis is one of the main pathology of neurodegenerative diseases.Whether the lipid in the plasma of hyperlipidemia through the blood-brain barrier toincrease the lipid in brain and thus induce the occurrence of neurodegenerativediseases by effect apoptosis, and the possible mechanism has not proved.ObjectiveTo study the effects of Hyperlipidemia on the pathological changes of the braintissue of New Zealand rabbits, apoptosis, expression of PCSK9and LDLR, and tostudy the possible mechanism of high cholesterol diet in inducing neurodegenerativediseases.Methods12healthy purebred New Zealand rabbits of12-month-old, male or female, weredivided into two groups randomly with6in each group, one group were fed withnormal diet and the other were fed with high cholesterol diet. All the rabbits werekilled after seven months. Triglycerides, total cholesterol, low density lipoproteinand high density lipoprotein in plasma is measured; HE staining and Oil red Ostaining were used to detect the pathological changes of cerebrum and cerebellum;Hoechst33258staining and flow cytometry were used to detect apoptosis ofcerebrum and cerebellum; The mRNA of LDLR in cerebrum and cerebellum wasanalyzed by RT-PCR, and the protein of PCSK9was analyzed by Western blotting.ResultThe triglycerides, total cholesterol, low density lipoprotein and high densitylipoprotein in plasma were significantly increased in the group with high cholesteroldiet than in the group with normal diet (P <0.05). HE staining showed that morphology of cerebrum and cerebellum in high cholesterol diet group changedsignificantly than in the group with normal diet,Oil red O staining showed thatstaining of cerebrum and cerebellum in high cholesterol diet group increased thanthe other group, Hoechst33258staining and flow cytometry showed that apoptosisrate of cerebrum and cerebellum in both group were very low, a slight increase inthe high cholesterol diet group than in the normal diet group. The mRNA expressionof LDLR of the high fat diet group was decreased compared to the other group (P<0.05), expression of PCSK9protein was increased in the high cholesterol dietgroup than in the normal diet group.ConclusionHigh cholesterol diet can increase the lipid in plasma in New Zealand rabbitsand caused hyperlipidemia, the pathomorphology of brain tissue has changed. Thelipid in the brain tissue of the high cholesterol diet group increased, highcholesterol diet can increase apoptosis rate slightly, PCSK9and LDLR may play arole in the development of neurodegenerative diseases caused by high cholesteroldiet.