Influcance Of Atorvastatin On Inflammatory Factor Of Frontal Cortex In Early Alzheimer's Disease Rat Model

Objective: In this experiment , we selected the ovarectomized rats injected with D-gal as the subject to observe the effect of atorvastatin , vitamin C+E and Inula Britannica on IL-6﹑TNF-α﹑SOD2﹑CAT﹑Bcl-2 and Bax .Methods1 Animals and groups40 female SD rats aged four months were randomly divided into two groups : Sham operated group ( Sham group ) , ovariectomized group ( OVX group ) . Sham group was ablated some adipose tissue above ovaries ; OVX group was ablated two sides ovaries . Rats in OVX received D-gal ( 20 mg in 0.5 ml 0.9% saline intraperitoneal injection everyday ) ; rats in Sham received saline (0.5 ml 0.9% saline intraperitoneal injection everyday ), after two weeks of ovariectomy .The rats in OVX were divided into four groups after six weeks of intraperitoneal injection : one group was intragastric administered with atorvastatin for 7.2 mg/kg·d ( ODA group ) ; the second group was intragastric administed with Vc for 45 mg/kg·d and Ve for 27 mg/kg·d ( ODV group ) ; the third group was intragastric administed with Inula Britannica for 0.9 g/kg·d (ODI group ) ; the last group was intragastric administed with distilled water for 1.5 ml/kg·d ( OD group ) . The Sham group was intragastric administed with distilled water for 1.5 ml/kg·d, too. Intragastric administration was to last 4 weeks and then sacrificed all rats.2 behavioral testsFour weeks after intraperitoneal injection, beheavioral tests were carried out to evaluate learning and memory abilities by Morris water maze . Four escape trails were given to all mice per day for four consecutive days. The same procedure was repeated for one day , after six weeks intraperitonea injection and four weeks of medicine administered orally . The escape latency was recorded.3 Tissues and data determiningTo anesthetize rats, frontal cortex were quickly separated and deep freezed in liquid Nitrogen.Then tissues were stored at -80℃to extract total RNA and protein. frontal cortex total RNA were extracted by Trizol regent. The relative mRNA contents ( IL-6﹑TNF-α﹑SOD2 and CAT ) were measured by RT-PCR usingβ-actin as inner standard. Protein quantity was measured by Bradford, expressed in mg/ml. The relative protein content of Bcl-2 and Bax were measured by western-blotting using andβ-actin as inner standards.Results1 Changes of learning and memory abilities Data from morris water maze showed that the escape latency was longer in the OVX+D-gal groups compared with the Sham group (P<0.05). The escape latency was shorter significantly in the ODA+ODV+ODI groups compared with the OD group (P<0.05).2 The relative expression of IL-6 in frontal cortex Compared with Sham, the level of IL-6 mRNA of OD was higher . Compared with OD, the level of IL-6 mRNA of ODA, ODV and ODI was lower .3 The relative expression of TNF-αin frontal cortexCompared with Sham, the level of TNF-αmRNA of OD was higher . Compared with OD, the level of TNF-αmRNA of ODA, ODV and ODI was lower .4 The relative expression of SOD2 in frontal cortexCompared with Sham, the level of SOD2 mRNA of OD was lower . Compared with OD, the level of SOD2 mRNA of ODA, ODV and ODI was higher .5 The relative expression of CAT in frontal cortexCompared with Sham, the level of CAT mRNA of OD was lower . Compared with OD, the level of CAT mRNA of ODA and ODV was higher, the level of CAT mRNA of ODI was no difference .6 The relative expression of Bcl-2 protein in frontal cortexCompared with Sham , the relative expression of Bcl-2 of OD,ODA,ODV,ODI was lower , and there was no difference between ODA, ODV, ODI and OD.7 The relative expression of Bax protein in frontal cortexCompared with Sham , the relative expression of Bax of OD was higher , Compared with OD, the relative expression of Bax of ODA, ODV, ODI was lower .Conclusion1 Data from morris water maze showed that the learning and memory abilities of the rats was impaired in the OVX+D-gal groups compared with the Sham group . The learning and memory impairment was attenuated significantly in the ODA, ODV and ODI groups .2 Atorvastation, Vc+Ve and Inula Britannica may improve inflammation and oxidative stress in this model of Alzheimer's disease.3 Compared with Sham, the relative expression of Bcl-2 was lower, the relative expression of Bax was higher in OD groups. After medicine administered , the relative expression of Bcl-2 of OD, ODA, ODV and ODI was no difference. But compared with OD , the relative expression of Bax of ODA, ODV, ODI was lower. The data suggests that the different medicines may imp- rove apoptosis through regulate the proapoptotic protein Bax.