| Objective: The aim of this study was to observe the efficacy of dexamethasone and temozolomide in the treatment of peritumoral edema of Glioma and to explore their mechanisms.Information and methods:1.Clinical trialIn this study,5-7 Glioblastoma multiforme patients underwent surgery.T2 WI sequence MRI images were collected after operation.We chose patients with severe peritumoral edema to take temozolomide orally for postoperative chemotherapyon the third day after operation.Shoot the MRI again to observe the changes of brain edema volume after three days.We also used ELISA test to detect the changes of edema related factors MMP-9,AQP-4 and VEGF in cerebrospinal fluid before and after chemotherapy.2.Animal experiment:We used the method of extracranial freezing to make the SD rat model of angiogenic brain edema.The rat model was randomly divided into blank control group(non operation group),operation control group(normal saline treatment group),temozolomide group,dexamethasone group and temozolomide dexamethasone combined treatment group.On the first day after the model was made,the rats were examined by brain MRI.After the model was proved to be successful,they were divided into groups and given drug intervention.After 3 days of treatment,the model underwent cranial MRI.We observed the changes of brain edema in the same rat before and after treatment,and collected the T2 WI sequence of rat brain MRI,The volume of brain edema in rats before and after treatment was measured by itk-snap software,and the volume ratio of edema regression was calculated,The dosage of temozolomide was 25 mg / kg by gavage and dexamethasone was 8mg / kg by tail vein every day,The experimental animals were killed on the first day of successful modeling and the third day after grouping treatment,The brain tissues of the experimental animals were collected.The changes of VEGF,MMP9 and AQP4 related edema factors in the edematous brain tissues of rats in each experimental group were detected by immunohistochemistry,Western blot and PCR.Results:1.The MRI images of glioblastoma patients after operation were collected.T2 WI sequence showed high signal intensity and obvious brain edema in the left temporal occipital lobe of the operation area,The patient took temozolomide orally on the 3rd day after operation.MRI showed that the volume of brain edema was significantly lower than that on the 3rd day after operation(P < 0.01).ELISA test was used to detect the changes of MMP-9,AQP-4 and VEGF in cerebrospinal fluid before and after chemotherapy.The results showed that the concentration of these factors decreased significantly after chemotherapy(P < 0.01)2.Using the method of extracranial freezing,the SD rat model of angiogenic brain edema was made.On the first day after the model was made,the rat brain tissue was examined by MRI.T2 WI sequence showed the high signal of brain tissue in the frozen area,suggesting the formation of brain edema;We dissected and took out the brain tissue of rats and found that the round light red frostbite focus,brain swelling,flattened gyrus and shallow sulcus;Evan blue staining showed the blue staining edema zone around the frozen area,which confirmed that the model of angiogenic brain edema was successfully made and the technology was stable.3.The same model was tested by MRI on the first day after successful modeling and the third day after treatment.The T2 WI sequence imaging data were collected,and the brain edema volume of rats before and after treatment was measured by ITK-snap software.The volume ratio of edema regression was calculated.It can be seen that the decrease of edema volume in dexamethasone group was the highest(P < 0.01)Temozolomide group decreased in turn,but there was no significant difference(P >0.05).The decrease of edema volume in normal saline group was the lowest.4.The results of immunohistochemistry showed that the expression of VEGF,MMP9 and AQP4 in normal saline group was the highest;The expression of VEGF,MMP9 and AQP4 in brain tissue of edema area in dexamethasone group was significantly lower than that in normal saline group(P < 0.01),and then decreased in Temozolomide + dexamethasone group and temozolomide group,but there was no statistical significance(P > 0.05)5.Western blot showed that the expressions of VEGF,MMP9 and AQP4 in brain tissue of rats with edema were significantly higher than those in sham operation group;After 3 days of treatment,the expression of VEGF,MMP9 and AQP4 in brain tissue of edema area in dexamethasone group decreased significantly(P < 0.01),followed by temozolomide + dexamethasone group,temozolomide group and normal saline group(P > 0.05,P > 0.05,P > 0.05)6.The results of q PCR showed that the expressions of VEGF,MMP9 and AQP4 in rat brain tissue after successful modeling were significantly higher than those in sham operation group;After 3 days of treatment,the expression of VEGF,MMP9 and AQP4 in brain tissue of edema area in dexamethasone group decreased significantly(P < 0.01),followed by temozolomide + dexamethasone group,temozolomide group and normal saline group(P > 0.05,P > 0.05,P > 0.05).Conclusion:1.The method of extracranial freezing was used to make the model of angiogenic brain edema in SD rats.The technology was mature and the effect was positive.2.Brain tumor related brain edema is a kind of mixed brain edema,which is composed of angiogenic brain edema and cytotoxic brain edema,but angiogenic edema is not the main factor in the formation mechanism of peritumoral edema.3.Dexamethasone can reduce the expression of VEGF in edematous brain tissue by reducing AQP-4 and MMP-94.Temozolomide has no obvious therapeutic effect on simple angiogenic edema.It may treat peritumoral edema of glioma by reducing cytotoxic edema produced by tumor cells. |
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