Study Of Correlation Between Expression Of Endocannabinoid Metabolic Enzyme And Pathological Grade In Brain Glioma

Objective: To study the expression of endocannabinoid metabolic enzyme FAAH and MAGL in different pathological grade brain glioma,and investigate the correlation between the expression of FAAH or MAGL and the pathological grade of glioma, in order to seek early reference index of determing biological characteristics of brain glioma and search for new therapeutic targets of brain glioma, also for providing a theoretical basis of the endocannabinoid system anti-glioma treatment.Methods: The experimental specimens were divided into normal brain tissue, low grade brain glioma (WHOâ… ~â…¡grade) and high grade brain glioma (WHOâ…¢~â…£grade).Normal brain tissues were obtained from traumatic brain injury patients undergoing decompression surgery. First, Applying quantitative real-time PCR(qRT-PCR) to detect the mRNA expression of FAAH and MAGL in 23 cases of human brian glioma tissues and 8 cases of normal brain tissues, and analyzed their correlation with pathological grade. Second, Applying high performance liquid chromatography-mass spectrometry to detect the activity of MAGL and FAAH in brain glioma tissues and normal brain tissues, in order to further investigate the correlation between the activity of FAAH or MAGL and the pathological grade of glioma.Results: 1.The FAAH mRNA was expressed in normal brain tissues and brain glioma tissues by qRT-PCR. FAAH mRNA in normal brain tissue, low grade brain glioma (WHOâ… ~â…¡grade) and high grade brain glioma (WHOâ…¢~â…£grade) were significant difference (P<0.01), and Accompany with the pathological grade, FAAH mRNA expression decreased (r=-0.552,P<0.01).2.The MAGL mRNA was detected in normal brain tissues and brain glioma tissues by qRT-PCR. The expression of MAGL mRNA in normal brain tissue, low grade brain glioma(WHOâ… ~â…¡grade) and high grade brain glioma (WHOâ…¢~â…£grade) were significantly different (P<0.01), and Accompany with the pathological grade, MAGL mRNA expression decreased(r=-0.586,P<0.01).3.The FAAH Activity was detected in normal brain tissues and brain glioma tissues by HPLC-MS. The Activity of FAAH was significantly different in normal brain tissue, low grade brain glioma(WHOâ… ~â…¡grade) and high grade brain glioma(WHOâ…¢~â…£grade) (P<0.01), and FAAH Activity decreased with the pathological grade(r=-0.65,P<0.01).4.The MAGL Activity was detected in normal brain tissues and brain glioma tissues by HPLC-MS. The Activity of MAGL was significantly different in normal brain tissue, low grade brain glioma(WHOâ… ~â…¡grade) and high grade brain glioma(WHOâ…¢~â…£grade) (P<0.01), and MAGL Activity decreased with the pathological grade(r=-0.37,P<0.01).Conclusions:1.FAAH mRNA and MAGL mRNA were expressed in brain glioma tissues and normal brain tissues, and was negatively related to the pathological grade of glioma. Therefore, Detecting FAAH mRNA and MAGL mRNA was significant for evaluating glioma malignancy.2.FAAH enzyme and MAGL enzyme were detected in brain glioma tissues and normal brain tissues, and FAAH enzyme and MAGL enzyme activity was negatively correlated with the pathological grade of glioma. Consequently, further testing the activity of FAAH enzyme and MAGL enzyme was significant for evaluating biological behavior of glioma.3.MAGL gene expression and enzyme activity were higher than FAAH in the same tissue.4.It is validated that high pressure liquid chromatographymass spectrometry can detect the activity of FAAH and MAGL in normal brain tissues and brain glioma tissues.