Experimental Study Of Treating Glioma By Intranasal Brain Targeting Of Resveratrol

Objective: By comparing the effect of intranasal and oral administration of resveratrol to glioma,to provide the preliminary basic research for clinical application of intranasal brain targeting of resveratrol to glioma.Methods: 1.We have established the orthotopic implantation model of human glioma cells in nude mice,10 days later,mice were randomly divided into 4 groups,(1)Nasal administration group: intranasal administration of resveratrol(n=20);(2)intragastric administration group: intragastric administration of resveratrol(n=20);(3)vehicle-treated group: intranasal administration of sodium carboxymethyl cellulose solution(CMC-Na)(n=20);(4):vehicle-treated group: intragastric administration of CMC-Na(n=20),with 10 mg/kg body weight doses of resveratrol for consecutive 10 days,the vehicle control groups were given the same amount of solvent.The general manifestation and survival time of different mice were observed after administration.Comparing the tumor size by HE staining and MRI.2.the microvessel density(MVD)and the expression of antigen Ki67,vascular endothelial growth factor(VEGF)and CD31 protein were detected using immunohistochemistry.The apoptosis of the tumor cells was evaluated with TUNEL assay.Results:1.The result of tumor size by HE staining is consistent with the MRI test: intragastric vehicle group(24.25±15.53)?nasal vehicle group(23.62±14.87)?intragastric administration group(13.00±4.80)?nasal administration group(9.87±2.55),the difference was significant,(intragastric vehicle group have no significant difference compared to nasal vehicle group).2.The survival time of 4 groups nude mice: The survival time of all the nude mice in the intragastric vehicle group is 43 days after tumor inoculation,while the intranasal vehicle group is 45 days.At the same time there was one survival mice in the intragastric administration group on the 63 th day after tumor inoculation,and there were 3 survival mice in the nasal administration group,the 4 nude mice were sacrificed artificially,and draw the survival curves.3.The analysis of Ki67 expression in tumor tissue: Comparing the Ki67 antigen labeling index(LI)of tumor tissue in the 4 groups,the results show that nasal administration group(17.50±2.75)was significantly lower than the intragastric administration group(35.75±4.12),intragastric administration group(35.75±4.12)was significantly lower than the nasal vehicle group(69.65±10.18)and the intragastric vehicle group(79.88 ± 5.87),which had significantly statistical difference(P=0.005).4.The analysis of VEGF expression in tumor tissue: the VEGF expression and angiogenesis of nasal administration group were the least,followed by the intragastric administration group and the two vehicle control group.The VEGF IRS scores: nasal administration group(14.23±1.04),intragastric administration group(28.10±3.77),nasal vehicle group(58.20±4.23),intragastric vehicle group(64.90±2.91),which had significantly statistical difference(P=0.018).5.The analysis of MVD positive staining microvessel number: The MVD positive staining microvessel number from low to high is nasal administration group(19.03± 2.64),intragastric administration group(35.33 ± 6.40),nasal vehicle group(67.93 ± 3.85),intragastric vehicle group(77.35 ± 4.45),which had significantly statistical difference(P=0.000).6.Results of TUNEL test showed that,the apoptosis rate of tumor cells in the treatment group was higher than that of the control group,also the control group was higher than that of the two vehicle control groups,which had significantly statistical difference(P<0.05).The number of apoptotic cells of 4 groups from low to high is intragastric vehicle group(6.63±2.54),nasal vehicle group(9.95±3.55),intragastric administration group(20.91 ± 5.18),nasal administration group(40.18±4.71).Conclusion: 1.Commpared with intragastric administration of resveratrol,treating glioma by intranasal brain targeting of resveratrol could inhibit the growth of glioma,prolong survival time of tumor-bearing nude mice and improve the quality of life.2.Intranasal brain targeting of resveratrol is by inhibiting the proliferation of glioma cells,reducing glioma angiogenesis and induce tumor cell apoptosis and other ways to achieve the purpose of the treatment of glioma.