本文選題：雌激素　切入點(diǎn)：雄激素　出處：《河北醫(yī)科大學(xué)》2010年碩士論文

【摘要】： 目的:白內(nèi)障是一種生理性衰退性疾病,是老年人致盲失明的主要原因。據(jù)統(tǒng)計(jì),50-60歲人群的患病率為60%-70%,70歲以上人群高達(dá)80%,且常為雙眼患病。不同類型的白內(nèi)障,其致病危險(xiǎn)因素及發(fā)病機(jī)制亦不同。但氧化損傷是白內(nèi)障發(fā)生的啟動(dòng)因素。許多實(shí)驗(yàn)都證明晶狀體的氧化損傷發(fā)生在晶狀體混濁之前。流行病學(xué)已有調(diào)查,絕經(jīng)后婦女發(fā)病率高于同年齡的男性,而且雌激素替代治療有助于延緩白內(nèi)障的發(fā)展。近些年,性激素尤其是雌激素在白內(nèi)障中的作用逐漸引起人們的重視,成為研究的熱點(diǎn)。 本實(shí)驗(yàn)通過(guò)對(duì)雌性性成熟Wistar大鼠行雙側(cè)卵巢切除術(shù)(ovariectomy, OVX),模擬人工絕經(jīng)狀態(tài),并給予大鼠雌、雄激素局部及全身應(yīng)用,觀察晶狀體有無(wú)混濁或混濁程度的變化,分析去勢(shì)雌鼠晶狀體氧化系統(tǒng)指標(biāo)含量的變化及其與血清中雌、雄激素水平的關(guān)系,同時(shí)對(duì)雌、雄激素及其不同的給藥途徑對(duì)去勢(shì)雌鼠晶狀體影響的差異進(jìn)行比較,進(jìn)而為探討絕經(jīng)后婦女白內(nèi)障相對(duì)高發(fā)病率這一臨床調(diào)查結(jié)果提供實(shí)驗(yàn)依據(jù)及理論基礎(chǔ)。 方法:清潔級(jí)健康成年雌性性成熟Wistar大鼠56只,3月齡,體重230-250克,無(wú)眼部疾病。隨機(jī)分為正常對(duì)照組8只(A)、假手術(shù)組8只(B)、實(shí)驗(yàn)組40只(C-G)。假手術(shù)組打開(kāi)腹腔后只切除部分脂肪,不切除卵巢。實(shí)驗(yàn)組隨機(jī)分為去勢(shì)組(C)及治療組(D-G):雌二醇點(diǎn)眼治療組(D)、全身雌二醇注射治療組(E)、睪丸酮點(diǎn)眼治療組(F)、全身睪丸酮注射治療組(G),每組8只,并行雙側(cè)OVX。去勢(shì)組僅行OVX,不給予任何藥物干預(yù),治療組自術(shù)后5個(gè)月開(kāi)始給藥,D組給予苯甲酸雌二醇注射液點(diǎn)雙眼,每日4次;E組給予苯甲酸雌二醇注射液200ug/kg/次肌肉注射,每3天一次;F組給予2.5%丙酸睪丸酮點(diǎn)雙眼,每日4次;G組給予丙酸睪丸酮3.75mg/kg/次肌肉注射,每3天一次,給藥時(shí)間均為6周。6周后處死動(dòng)物,立刻取所有大鼠晶狀體以測(cè)其超氧化物歧化酶(superoxide dismutase,SOD)、谷胱苷肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)、水溶性蛋白(water-soluble protein,WSP)的含量。各組分別于術(shù)前、術(shù)后第5個(gè)月及給藥6周后測(cè)大鼠血清雌二醇及睪酮水平。實(shí)驗(yàn)期間每周于裂隙燈下檢查各組大鼠晶狀體的變化。比較本實(shí)驗(yàn)所實(shí)施的OVX及雌、雄激素不同途徑治療后所引起雌、雄激素含量變化對(duì)晶狀體混濁程度及晶狀體氧化系統(tǒng)各指標(biāo)的含量有無(wú)影響。實(shí)驗(yàn)數(shù)據(jù)用應(yīng)用SPSS13.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)處理。 結(jié)果:1 OVX術(shù)后5個(gè)月大鼠血清中雌二醇、睪酮水平較術(shù)前明顯下降(P0.01);全身苯甲酸雌二醇(E組)及丙酸睪丸酮(G組)補(bǔ)充6周后其含量較OVX術(shù)后升高(P0.01),經(jīng)點(diǎn)眼途徑(D、F組)補(bǔ)充后含量變化不明顯(P0.05)。 2每周裂隙燈顯微鏡下觀察大鼠晶狀體,未發(fā)現(xiàn)皮質(zhì)空泡、水裂、板層分離、楔形混濁、前囊點(diǎn)狀混濁甚至核性及后囊膜下混濁等。 3晶狀體SOD的含量:去勢(shì)組(C)大鼠晶狀體SOD含量明顯低于A和B組(P0.01);全身苯甲酸雌二醇治療6周后E組晶狀體SOD含量明顯高于C組(P0.01);全身丙酸睪丸酮治療6周后G組晶狀體SOD含量較C組降低(P0.05);雌、雄激素點(diǎn)眼組(D、F)與C組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 4晶狀體GSH的含量:C組大鼠晶狀體GSH含量明顯低于A和B組(P0.01);E組晶狀體GSH含量高于C組(P0.05);G組晶狀體GSH含量較C組降低(P0.05);D、F組與C組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 5晶狀體MDA的含量:C組大鼠晶狀體MDA含量明顯高于A和B組(P0.01);E組晶狀體MDA含量明顯低于C組(P0.01);D、F、G組與C組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 6晶狀體WSP的含量:C組大鼠晶狀體WSP含量明顯低于A和B組(P0.01);E組晶狀體WSP含量明顯高于C組(P0.01);D、F、G組與C組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論:1切除雌鼠雙側(cè)卵巢5及6.5個(gè)月后均未見(jiàn)晶狀體混濁,說(shuō)明去勢(shì)較長(zhǎng)一段時(shí)間尚不能引起臨床所見(jiàn)的白內(nèi)障形成。 2去卵巢大鼠晶狀體氧化系統(tǒng)各指標(biāo)的變化表明了氧化損傷處于白內(nèi)障發(fā)病機(jī)制中的早期。OVX所致性激素水平的改變可加重晶狀體的氧化損傷。 3全身應(yīng)用雌激素可增強(qiáng)晶狀體SOD活性,提高GSH、WSP水平,降低MDA含量;全身雄激素應(yīng)用減弱了晶狀體SOD活性,降低了GSH水平,對(duì)MDA、WSP含量尚無(wú)明顯影響。雌激素可對(duì)抗晶狀體的氧化損傷,對(duì)其具有保護(hù)作用;而雄激素則在一定程度可能加速了去勢(shì)雌鼠晶狀體氧化損傷的發(fā)展 4雌、雄激素不同的給藥途徑對(duì)大鼠晶狀體的影響不同,全身應(yīng)用的作用大于局部點(diǎn)眼途徑。
[Abstract]:Objective: cataract is a physiologic degenerative illness, is a major cause of blindness in older people blind. According to statistics, the 50-60 year old population prevalence rate was 60%-70%, 70 people over the age of up to 80%, and often eyes disease. Different types of cataract, the risk factors and pathogenesis but oxidation are also different. Damage is the initiation factor of cataract. Many experiments have proved that oxidative damage occurs in the lens opacity. Before the existing epidemiological survey, postmenopausal women had higher incidence rate than men of the same age and estrogen replacement therapy contributes to delaying cataract. In recent years, especially the role of estrogen in sex hormone in cataract has gradually attracted people attention, has become a hot research topic.
In this experiment, female Wistar rats underwent bilateral ovariectomy (ovariectomy, OVX), artificial menopause state, and rats were given estrogen, androgen local and systemic application, there is no change of lens opacity or opacity, changes of crystalline body oxidation system in ovariectomized rats and serum and its content index female, relationship between androgen levels, while the female, to compare the differences of androgen and different routes of administration on ovariectomized rats lens effect, and then explore postmenopausal women with relatively high incidence of cataract in this clinical investigation results provide experimental basis and theoretical basis.
鏂規(guī)硶:娓呮磥綰у仴搴鋒垚騫撮泴鎬ф，

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