To Investigate The Effect Of Durian On Blood-Brain Barrier Permeability Based On The Ratio Of Caveolin-1 And AQ In Cerebrospinal Fluid

Objective:1.To understand the main compounds contained in the volatile substances of durian meat extract and whether they have the effect of changing the permeability of the Blood–brain barrier,and if so,whether they contain substances similar to Muscone in chemical structure.2.To detect whether the permeability of musk and durian meat extracts to the Blood–brain barrier of rats under physiological conditions and whether their mechanisms are related to MMP-9.3.To understand whether musk and durian meat can protect and regulate the permeability of Blood–brain barrier in the clinical application of patients with Subarachnoid hemorrhage.And whether its possible mechanism of action is related to caveolin-1.4.Compare the effect of musk and durian meat on the permeability of Blood–brain barrier,and lay a foundation for the development of new drugs to regulate the permeability of Blood–brain barrier.Animal experiment:refer to the conventional boiling method of Chinese medicine,use Ultrapure water as solvent,use ultrasonic extractor to prepare durian meat extract,freeze dry it and send it for inspection,use gas chromatography-mass spectrometry（GS-MS）to detect the volatile substances in durian meat extract.Reserve the remaining durian meat extract for later use.Twenty rats were randomly divided into four groups with five rats in each group,which were defined as blank group,control group（Muscone group）,low-dose durian meat group,and high-dose durian meat group.After feeding the corresponding reagents,inject BE dye solution into the tail vein,cut off the head and remove the brain,peel off the meninges,and observe the staining of the brain tissue.Finally,Western Blot was performed to examine the expression level of MMP-9 in rat brain tissue.Clinical experiment:120 patients with Subarachnoid hemorrhage are expected to be included and randomly divided into blank group,control group（artificial musk group）,low-dose durian meat group and high-dose durian meat group according to the order of admission.The blank group received routine treatment as mentioned above.The control group was given0.05gqd of artificial musk by oral administration or intragastric injection for seven consecutive days,while the observation group 1 was given 40g qd of durian meat by oral administration or intragastric injection for seven consecutive days.The observation group 2 was given 100g qd of durian meat by oral administration or intragastric injection for seven consecutive days.Collect cerebrospinal fluid and serum samples within 48 hours of admission and 7 days after intervention,and check the content and ratio of Caveolin-1,albumin,and blood cell content.To indirectly compare the effects of volatile substances from musk and durian meat on the permeability of Blood–brain barrier in patients with Subarachnoid hemorrhage,and explore whether the mechanism of their effects is related to the expression of Caveolin-1.Results:1.The GS-MS analysis of durian meat extract showed that there were 46 compounds,and alkanes accounted for a high proportion,of which the relative content of 3,5-dimethyl-1,2,4-triathio Cyclopentane was the highest,18.49%.There was no substance similar to Muscone structure in durian meat extract.2.In animal experiments,there was no significant color change in the brain tissue of normal rats in each group after staining,and there was no statistically significant difference in MMP9 comparison between the groups（p>0.05）.3.A total of 120 cases were included in the clinical study,including 33 deaths and shedding.Finally,87 cases were collected,including 35 male cases and 52 female cases.The male to female ratio was 1:1.48,with an age range of 36 to 93 years old and an average age of 63 years old.There was a significant difference in the overall mean between the Muscone group and the other treatment groups（p<0.05）,while there was no significant difference in the other three groups.Conclusion:1.The GS-MS analysis of durian meat extract shows that there are 46 compounds in total,and alkanes account for a high proportion,of which the relative content of 3,5-dimethyl-1,2,4-triathio Cyclopentane is the highest,18.49%.There is no substance similar to Muscone structure in durian meat extract.2.In animal experiments,there was no significant color change in the brain tissue of normal rats in each group after staining,and there was no statistically significant difference in MMP-9 comparison between the groups（p>0.05）.It was not confirmed that the volatile substances in the extract of Eclipta granatum had an impact on the permeability of the Blood–brain barrier（BBB）.Compared to previous studies by Xu Qiuying et al.^[1]on pathological changes in rats,artificial musk can downregulate the expression of MMP-9 in brain tissue of rats with focal cerebral ischemia-reperfusion.In this study,Muscone（the main active ingredient of musk）has no effect on the expression of MMP-9 in normal rat brain tissue under physiological conditions.It indicates the two-way regulation of musk（under physiological conditions,it can enhance the permeability of Blood–brain barrier BBB,so that therapeutic drugs can more easily penetrate the BBB,and improve drug utilization;under pathological conditions,it can inhibit the expression of MMP-9 in brain tissue,reduce the damage of cerebrovascular and Blood–brain barrier,and reduce brain damage and brain edema）.Under physiological conditions,it can promote the penetration of drugs into the Blood–brain barrier without changing or increasing the expression of MMP-9,The penetration promoting effect under physiological conditions is not significantly correlated with MMP9.And durian meat extract has not been proven to have a penetration promoting effect under physiological conditions.3.In clinical experiments,artificial musk has a significant regulatory effect on AQ ratio and Caveolin-1 in cerebrospinal fluid of patients with Subarachnoid hemorrhage,has a certain protective effect on brain tissue after injury,and has a certain impact on BBB permeability of Blood–brain barrier.However,durian meat extract group has no significant regulatory effect on AQ ratio and Caveolin-1 in cerebrospinal fluid of patients with Subarachnoid hemorrhage,and it has not been proved that it has an impact on BBB permeability of Blood–brain barrier,and has not been proved to have a protective effect on Blood–brain barrier under pathological conditions.