A Study Of Combined Aquaporin-4 SiRNA With Hypothermia Treatment On Cerebral Edema Following Traumatic Brain Injury In Rats

Object:To optimize the treatment effect of siRNA targeting aquaporin 4 with hypothermia on cerebral edema following traumatic brain injury in rats.Methods:To construct siRNA targeting aquaporin 4, and establish the TBI models in rats. The animals were divided into four groups:TBI group, AQP4 siRNA group, hypothermia group, and combined group. To extract the total mRNA and proteins on the 1st,3rd,5th, and 7th day for RT-PCR and western blot analysis. The changes of brain water content and permeability of blood-brain barrier were measured by the methods of wet and dry weight and Evans blue fluorometry. All the rats were given a mark for their nerve function on the 7th day.Results:(1) Compared with the control group rats, the other three groups all get better result of nerve functional defect 7ds after TBI (P<0.05), while it seems that combining hypothermia treatment with AQP4 siRNA has the best effect (P<0.05).(2) Compared with the hypothermia treatment group rats, the AQP4 siRNA treatment group get better effect in silencing AQP4 mRNA and restrainting AQP4 protein expression both from the RT-PCR test and Western Blot test (P<0.05), but the group of combining hypothermia treatment with AQP4 siRNA is the best way (P< 0.05).(3) Comparison of brain water content in the three treated groups shows hypothermia treatment is better than the AQP4 siRNA, but not as good as the combining group (P<0.05).(4) All the three treated groups showed effect of changing the blood brain barrier in TBI rats according the Evans-blue test, while, hypothermia treatment is better than the AQP4 siRNA but less than the combining group (P<0.05).Conclusion:Hypothermia treatment can obtain better effect than AQP4 siRNA in lessening brain edema level. Meanwhile, siRNA treatment can obtain better effect than hypothermia group in silencing AQP4 mRNA and protein expression. When combining hypothermia treatment with AQP4 siRNA, we can obtain an optimized result than the single application of above mentioned two groups.The application of siRNA targeting aquaporin 4 may optimize the treatment effect of hypothermia on traumatic brain injury rats.