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The Intervention Of Decorin On Leptomeninge's Fibrosis Due To SAH

Posted on:2009-10-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:F LiuFull Text:PDF
GTID:1114360245983597Subject:Surgery
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Objective:Subarachnoid hemorrhage(SAH)is a common disease to neurology and neurosurgery,and chronic hydrocephalus is a common chronic complication after SAH.Leptomeninges include aracnoid mater, pia mater and subarachnoid space,arachnoid cell is a kind of specific fibroblast.TGF-β1 can modulate positively fibroblast functions of proliferation and secretion.After SAH,the elevation of TGF-ββ1 level in cerebrospinal fluid can lead to fibrosis of leptomeninges(aracnoid, subarachnoid space)and arachnoid villi,which result in chronic hydrocephalus. Decorin(DCN)is generally referred as a natural antagonist of TGF-β1 and have effect of anti-fibrosis.To a certain degree,it has realistic significance to choose DCN as precaution against chronic hydrocephalus in cases with SAH because the fibrosis of leptomeninges(aracnoid,subarachnoid space)and arachnoid villi might be diminished by DCN.Up to now,there is no reports on this field.The purpose of this study is to preliminary research the intervention of DCN on leptomeninges' fibrosis due to SAH.Methods:First,80 SD rats were randomly devided into blank group, normal salineⅠgroup(NSⅠgroup)and modelⅠgroup(SAHⅠgroup),to build up the animal models of SAH by twice injecting autoblood solution into the cisterna magna.At the 3rd,6th,10th,14th,21stday,rats were respectively killed,the brain of the 3rdwere observed to detect the blood clot in subarachnoid space,and the levels of TGF-β1 and PICP in collected CSF of all were measured to detect their dynamic variation,and lepomeninges of the 21stday's were measured to detect the fibrotic degree.Then,40 SD rats were randomly devided into experimental group, control group,SAHⅡgroup and NSⅡgroup.Decorin was injected into the cisterna magna of experimental group and control group at the 2nd,10TH.At the 21stday,we measured the levels of TGF-β1 and PICP in CSF, and the fibrotic degree of lepomeninges.The methods of measuring the fibrotic degree include collagen fiber Masson staining,RT-PCR measuring mRNA of CollagenⅠ(ColⅠ)and CTGF,Western-blot to measuring protein of ColⅠand CTGF.Results:1.Construction of animal model of SAIl:①At the 3rd, scattered blood clot could be observed in subarachnoid space and cisterna; Red blood cells could be observed in the space of leptomeninges between dura mater and brain tissue on microslides by Masson staining;②The levels of TGF-β1 in CSF of SAHⅠgroup rose statistically by double phase,compared with control group(P<0.01);③The levels of PICP in CSF of SAHⅠgroup were gradually increasing and obviously higher than that of NSⅠgroup after the 6th(P<0.01);④Masson staining showed that the gray scale of lepomenings in SAHⅠgroup was obviously lower than that of NSⅠgroup,and thickness was obviously higher(P<0.01);⑤The expressed level of mRNA of ColⅠ,CTGF and protein of ColⅠ,CTGF were obviously higher than that of NSⅠgroup(P<0.05);⑥There were no signicant difference between blank group and NSⅠgroup on these detected items(P>0.05).2.Intervention of DCN:①Experimental group VS SAHⅡgroup: the level of TGF-β1 in experimental group was a little declining but no signicant differences(P>0.05);the level of PICP was obviously decreasing in experimental group(P<0.05);Masson staining showed that thickness of lepomenings in experimental group was a little thinning but no signicant differences(P>0.05),while gray scale in experimental group was obviously increasing(P<0.05);the expressed level of ColⅠmRNA was obviously decreasing(P<0.05),while expressed the level of CTGF mRNA was a little decreasing but no signicant differences(P>0.05);the protein expressed level of ColⅠand CTGF were obviously decreasing (P<0.05).②Experimental group VS NSⅡgroup:the levels of TGF-β1 and PICP in experimental group were obviosly increasing(P<0.05); Masson staining showed that thickness of lepomenings in experimental group was obviously enlarging and gray scale was obviously decreasing (P<0.05);the expressed level of mRNA of ColⅠ,CTGF and protein of ColⅠ,CTGF in experimental group were obviously increasing(P<0.05);③Control group VS NSⅡgroup:no signicant difference on these detected items(P>0.05).Conclusion:1.The levels of TGF-β1 in CSF was increasing by double phase after SAH;2.At the 21stday,There were leptomeninges' fibrosis SAH;3.After the accident of SAH,DCN relieved leptomeninges' fibrosis.
Keywords/Search Tags:subarachnoid hemorrhage, leptomeninges, fibrosis, decorin
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