| Objective: By observing the effect of electroacupuncture on regional cerebral blood flow(r CBF)and behavior in rats with chronic cerebral hypoperfusion(CCH)model,the effect of electroacupuncture intervention on cognitive function of CCH model was explored;The changes of related components in SOCS3-JAK2/STAT3 signal transduction pathways were investigated for the mechanism of electroacupuncture in improving cognitive function in CCH rats model.Methods: Forty healthy Sprague-Dawley(SD)male rats were randomly split into 4 groups: Sham group,Modle group,Sham EA group,EA group,10 rats in each group.Before operation,the rats in each group were fed for two weeks,weighed,and then subjected to inhalation of isoflurane anesthesia.Establish the rat model of CCH by improving 2-VO surgery under isoflurane anesthesia.Sham group only treated with bilateral common carotid artery without ligation tretment.The second day after operation,rats received electroacupuncture treatment and balance treatment:the EA group treated by electroacupuncture at "Baihui","Dazhui",the stimulation frequency of electroacupuncture was continuous,frequency 15 HZ,intensity 1m A,time 30 min / time / day.Sham EA group only acupuncture without energized,Sham group and Modle group were received balance treatment(equal to the EA group grasping fixed)once a day,continuous intervention for 4 weeks.Behavioral tests were made at fourth week after the model was established,and then sacrificed by anesthesia.Observation index:(1)Testing changes of r CBF in each group at 4 time points: before modeling,after modeling for 30 minutes,after modeling for 2 weeks and after modeling for 4 weeks(before the death);(2)One week before the death,open field(OF),O-maze and Morris water maze(MWM)were used to detect spontaneous activity and learning and memory ability of rats in unfamiliar environment(3)The relative expression levels of SOCS3、P-JAK2、P-STAT3、i NOS and COX2 in the hippocampus were detected by Western blotting;(4)The positive expressions of P-JAK2 、 P-STAT3 in rats detected by immunoflurescence double labeling method.Result:1.r CBF test results: After CCH modeling,r CBF of rats in each group showed different degrees of decrease at discrete time points.Compared with Sham group at the same time point,model rats,Sham EA rats and EA rats r CBF decreased significantly(P <0.01).Compared with model group at the same time point,there was no significant difference in Sham EA group at postop(P> 0.05),Sham Compared with sham EA group,the r CBF of EA group and EA group were significantly increased at 1 week,2 weeks and 4 weeks after postop(P <0.01 or P <0.05).There was no significant difference in r CBF between the EA group and the EA group after 1week(P> 0.05),and there was a significant difference between the two groups(P<0.01 or P <0.05)2.Behavioral test results:(1)Results of orientation navigation trail: With the increase in training time,the escape latency of rats in each group showed a decreasing trend.There was no significantly difference between the groups in the first day.Compared with Sham group at the same time point,latency of rats in Modle group decreased slowly,with a significant difference at the second day to the fifth day(P <0.01).Latency of rats in Sham EA group decreased rapidly.with a significant difference at the second day to the fifth day(P <0.01 or P <0.05).Latency of rats in EA group decreased rapidly and the difference was statistically significant in the second and third days(P <0.05).There was no significantly difference at fourth day and fifth day(P> 0.05).Compared with Model group at the same time points,latency of rats in Sham EA group and EA group decreased rapidly,and have significant differences at the third day to the fifth day(P <0.01 or P <0.05).There was considerable difference at the 4th and 5th day(P<0.01).Compared with Sham EA group at the same time point,there was significant difference in latency at the 4th and 5th day with the EA group(P <0.05).(2)Reversal trial: Compared with Sham group,the exploring time of rats in Modle group and Sham EA group were significantly reduced(P <0.01),while there was no significant difference in exploring time with EA group(P> 0.05).Compared with Model group,the exploring time of rats in Sham EA and EA group are increased(P <0.01 or P <0.05).Compared with Sham EA group,the rats in EA group had longer exploration time,the difference was statistically significant(P <0.05).(3)Open-field test results: Compared with Sham group,the rats in Modle group and Sham EA group had shorter residence time,the difference was statistically significant(P <0.01),there was no statistical difference between EA group(P> 0.05).Compared with Modle group,there was no significant difference in retention time between Sham EA group,but the time of EA group was evidently increased(P <0.01).Compared with Sham EA group,The residence time in rats of EA group increased markedly(P <0.01).(4)O-maze test results: Compared with Sham group,the rats in Modle group and Sham EA group had shorter residence time,the difference was statistically significant(P <0.05),there was no statistical difference in stay time in EA group(P> 0.05).Compared with Modle group,there was no significant differences in residence time between Sham EA group(P> 0.05),but the time of EA group was evidently increased(P <0.01).Compared with Sham EA group,the residence time in EA group increased significantly(P <0.01).3.Western blot experimental observation results:(1)The expression of SOCS3,P-JAK2 and P-STAT3 in hippocampus: The expressions of P-JAK2 and P-STAT3 in CCH model rats after chronic cerebral ischemia were significantly increased,and the change of two groups are basically same.The expression of P-JAK2 and P-STAT3 in EA group were significantly decreased,while the expression of SOCS3 in EA group was significantly higher than that in other groups.(2)The expression of i NOS and COX2 protein in hippocampus: The relative expression of i NOS protein in Modle group was significantly higher than that in the Sham group and EA group(P <0.01).The COX2 result was in agreement with that of i NOS(P <0.05).4.Immunofluorescence showed that positive cells of P-JAK2 and P-STAT3 were detected in hippocampus CA1 area of each group.Conclusion:1.Electro-acupuncture can improve regional cerebral blood flow in CCH model rats.then improving anxiety emotion and cognitive ability.2.Electro-acupuncture can up-regulate the expression of SOCS3.Inhibit the P-JAK2 and P-STAT3,and down-regulate the expression of i NOS and COX2.3.Effect of Electroacupuncture on Cognitive Function of CCH model rats made effect by SOCS3-JAK2/STAT3 Signal Transduction Pathway. |
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