雄激素与干眼

干眼是眼科常见疾病,在人群中其患病率随年龄的增长而增加,女性更为常见.研究发现雄激素可影响泪膜的功能,可能影响干眼的发生.本文就雄激素对干眼的影响作一综述,旨在为进一步的研究以及临床应用奠定基础.     

雄激素与干眼

干眼是眼科常见疾病,在人群中其患病率随年龄的增长而增加,女性更为常见.研究发现雄激素可影响泪膜的功能,可能影响干眼的发生.本文就雄激素对干眼的影响作一综述,旨在为进一步的研究以及临床应用奠定基础.     

雄激素与干眼

干眼是眼科常见疾病,在人群中其患病率随年龄的增长而增加,女性更为常见.研究发现雄激素可影响泪膜的功能,可能影响干眼的发生.本文就雄激素对干眼的影响作一综述,旨在为进一步的研究以及临床应用奠定基础.     

密蒙花提取物滴眼对干眼症去势鼠泪腺组织雄激素受体数量的影响

目的:观察密蒙花提取物滴眼剂对去势所致干眼症雄鼠基础泪液分泌量、泪膜稳定性、泪腺中雄激素受体表达的影响,探讨密蒙花提取物滴眼剂抗雄激素水平下降所致干眼症的作用机制。方法:将45只Wister雄性大鼠随机分为空白组(A1、A2、A3)、模型组(B1、B2、B3)、密蒙花提取物滴眼剂治疗组(C1、C2、C3),共9组,1代表饲养1mo,2代表饲养2mo,3代表饲养3mo,每组5只,对B、C组行去势术建立动物模型,对C组以密蒙花提取物滴眼剂连续滴眼治疗1mo,对全部实验大鼠行Schirmer I试验、测量泪膜破裂时间,采用流式细胞仪检测泪腺中雄激素受体的表达。结果:C组Schirmer I试验测量值明显高于B组(P<0.01),泪膜破裂时间明显长于B组(P<0.01),显示密蒙花提取物滴眼剂能够显著维持泪腺基础分泌量和泪膜的稳定性;C组流式细胞仪检测的AR阳性表达率明显高于B组,显示密蒙花提取物滴眼剂中的有效成分可能有拟雄激素的效应。结论:密蒙花提取物滴眼剂中主要成分为黄酮类物质,可显著抑制雄激素水平降低后大鼠干眼症的发生,其作用机制可能与黄酮类物质结构与雄激素类似,可以起到拟雄激素效应,从而维持泪腺基础分泌量和泪膜的稳定性。     

去势雄兔干眼病模型角膜上皮细胞凋亡及相关基因表达的研究

目的　探讨去势雄兔干眼病模型角膜上皮细胞凋亡及相关基因表达与组织损伤的关系。方法　制作 6只去势雄兔干眼病模型 ,采用原位末端标记及免疫组织化学方法 ,对模型兔及 6只对照兔角膜上皮细胞中的凋亡细胞及Fas、FasL、Bax和bcl 2等相关基因蛋白的表达进行检测。结果　干眼病模型兔角膜上皮细胞凋亡数为 ( 5 2 3± 2 67)个 /高倍视野 ;对照兔为 ( 0 5 8± 0 13 )个 /高倍视野 (P <0 0 1)。模型兔角膜上皮细胞中 ,Fas、FasL及Bax阳性表达的细胞数均明显高于对照组 (P <0 0 1) ,与凋亡细胞数呈正相关 (r=0 78,0 82 ,0 76,P <0 0 5 ) ;bcl 2阳性表达的细胞数明显低于对照组 (P <0 0 1) ,与凋亡细胞数呈负相关 (r =-0 72 ,P <0 0 5 )。结论　去势雄兔角膜组织中上皮细胞凋亡可能是导致角膜变薄、干燥 ,进而功能丧失的原因之一 ;Fas、FasL及Bax的增加及bcl 2的减少均与促进细胞凋亡有关。     

鬼针草滴眼液预防去势雄兔干眼症的实验研究

目的　研究鬼针草滴眼液对雄兔去势所致干眼症的预防作用。方法　选取新西兰白兔２４只（２４眼,均为右眼）,制作去势雄兔干眼症模型,模型制作后即随机分为Ａ、Ｂ两组（各１２眼）:实验组（Ａ组）使用鬼针草滴眼液滴眼,对照组（Ｂ组）使用磷酸盐缓冲液（ｐｈｏｓｐｈａｔｅｂｕｆｆｅｒｅｄｓａｌｉｎｅ,ＰＢＳ）滴眼。另选取２只兔作为正常对照分别于治疗前和治疗后１周、２周、１个月及２个月进行ＳｃｈｉｒｍｅｒＩ试验（ＳｃｈｉｒｍｅｒＩｔｅｓｔ,ＳＩＴ）检查、角膜荧光素染色（ｆｌｕｏｒｅｓｃｅｉｎ,ＦＬ）,并进行泪液总蛋白含量、淀粉酶活性、乳铁蛋白、溶菌酶含量检测及角膜共聚焦显微镜扫描。结果　治疗前Ａ、Ｂ两组ＳＩＴ、ＦＬ评分、泪液总蛋白量、乳铁蛋白、溶菌酶及淀粉酶活性相比,差异均无统计学意义（均为Ｐ＞０．０５）;治疗１周、２周、１个月及２个月后,Ｂ组ＳＩＴ、ＦＬ评分较治疗前均稍有恶化,差异均有统计学意义（均为Ｐ＜０．０５）,而泪液总蛋白量、乳铁蛋白、溶菌酶及淀粉酶活性与治疗前相比差异均无统计学意义（均为Ｐ＞０．０５）;Ａ组ＳＩＴ、ＦＬ评分、泪液总蛋白量、乳铁蛋白、溶菌酶及淀粉酶活性均有不同程度改变,差异均有统计学意义（均为Ｐ＜０．０５）;Ａ、Ｂ两组各时间点ＳＩＴ、ＦＬ评分、泪液总蛋白量、乳铁蛋白、溶菌酶及淀粉酶活性相比,差异均有统计学意义（均为Ｐ＜０．０５）。治疗２个月后,Ａ组上皮基底细胞和炎症细胞密度分别为（４２６２±２６８）ｍｍ－２和（３１２±１０３）ｍｍ－２,而Ｂ组上皮基底细胞和炎症细胞密度分别为（３１０６±２３７）ｍｍ－２和（３２±２３）ｍｍ－２,两组比较,差异均有统计学意义（均为Ｐ＜０．０５）。结论　鬼针草滴眼液能有效预防雄激素水平降低所致兔干眼症。     

雌、雄激素对去卵巢大鼠泪腺中IL-6表达的影响

目的 探讨雌、雄激素对去卵巢大鼠泪腺中IL-6表达的影响.方法 3个月龄雌性Wistar大鼠64只,随机分为正常对照组8只、假手术组8只、实验组48只.实验组行双侧卵巢切除术(ovariectomy,OVX).实验组动物于术后5个月随机分为干眼模型组、赋形荆治疗组、全身雌二醇治疗组、雌二醇滴眼组、全身睾酮治疗组和睾酮滴眼组,每组8只大鼠.给药6周后处死动物,取其泪腺检测IL-6的含量.实验组分别于术前、术后5个月及给药后6周测大鼠血清雌二醇和睾酮水平.结果 OVX术后5个月大鼠血清雌二醇及睾酮水平均降低,手术前后比较差异均有统计学意义(均为P<0.05).全身睾酮治疗组治疗6周后泪腺中IL-6含量为(3561.50 ±173.68)×10-9·L-1,比干眼模型组(4075.63±305.81)×10-9·L-1降低(P<0.05).全身雌二醇治疗组治疗6周后泪腺中IL-6含量为(4 591.98±116.57)×10-9g·L-1,比干眼模型组升高,手术前后比较差异有统计学意义(P<0.05).结论 全身应用雄激素可减少去势雌鼠泪腺中IL-6的含量从而减轻泪腺炎症,全身应用雌激素可增加泪腺中IL-6的含量从而加重泪腺炎症.     

桑色素滴眼液治疗围绝经期雌性兔干眼的实验研究

目的:探究桑色素滴眼液在围绝经期雌性兔干眼症中的治疗作用。方法:选取雌性新西兰大白兔36只,采用双侧卵巢切除术,术后饲养60d,制作围绝经期雌兔干眼症模型(36眼,均为右眼),其中24只随机分成对照组、实验组两组(各12只):对照组应用磷酸盐缓冲液(PBS),实验组应用桑色素滴眼液,另12只不使用任何滴眼液。治疗前,治疗后2、4、6wk对实验兔采取角膜荧光素染色(FL)、Schirmer Ⅰ试验(SⅠt)检查,同时测验溶菌酶含量、乳铁蛋白、淀粉酶活性和泪液总蛋白含量,并使用角膜共聚焦显微镜观察。结果:治疗前两组的SⅠt、FL、溶菌酶含量、乳铁蛋白、淀粉酶活性和泪液总蛋白量均无差异(P>0.05);治疗2、4、6wk后,对照组和实验组SⅠt和FL评分发生了不同的变化(P<0.05)。实验组溶菌酶含量、乳铁蛋白、淀粉酶活性和泪液总蛋白量较治疗前没有显著变化(均P>0.05),对照组溶菌酶含量、乳铁蛋白、淀粉酶活性和泪液总蛋白量都发生了程度不一的变化(均P<0.05)。治疗后2、4、6wk时两组SⅠt、FL评分、溶菌酶含量、乳铁蛋白、淀粉酶活性和泪液总蛋白量均有差异(P<0.05)。治疗6wk,对照组炎症细胞密度为321±91个/mm^2,上皮基底细胞密度为4436±289个/mm^2,实验组炎症细胞密度为36±11个/mm^2,上皮基底细胞密度为3219±223个/mm^2,两组均有差异(P<0.05)。治疗6wk后,对照组角膜上皮下多支神经纤维发生弯曲,密度显著减少(P<0.05),实验组神经弯曲度明显减小,密度较治疗前增加。结论:桑色素滴眼液对围绝经期雌性兔干眼症具有明确的治疗作用。     

二氢睾酮对小鼠角膜上皮细胞Mucins表达的影响

目的　探讨不同浓度二氢睾酮（ＤＨＴ）对角膜上皮黏蛋白Ｍｕｃｉｎｓ表达的影响。方法　体外原代培养ＢＡＬＢ／ｃ小鼠角膜上皮细胞,分为空白对照组以及ＤＨＴ干预组,ＤＨＴ干预组给予不同浓度（０．０５ｇ?Ｌ－１、０．１０ｇ?Ｌ－１、０．２０ｇ?Ｌ－１、０．５０ｇ?Ｌ－１、１．００ｇ?Ｌ－１）ＤＨＴ干预２４ｈ;采用ＲＴ-ＰＣＲ方法与免疫荧光组织化学方法分别检测Ｍｕｃ１、Ｍｕｃ４ｍＲＮＡ以及蛋白水平的表达。结果　Ｍｕｃ１、Ｍｕｃ４ｍＲＮＡ检测结果显示:空白对照组,０．０５ｇ?Ｌ－１、０．１０ｇ?Ｌ－１、０．２０ｇ?Ｌ－１、０．５０ｇ?Ｌ－１ ＤＨＴ干预组Ｍｕｃ１ｍＲＮＡ相对表达量分别为１．００±０．００、０．１５±０．０１、１．４０±０．０９、０．０７±０．１１、０．０６±０．０２;Ｍｕｃ４ｍＲＮＡ相对表达量分别为１．００±０．００、０．３０±０．２８、１．３６±０．０５、０．４３±０．０１、０．４５±０．０１,０．１０ｇ?Ｌ－１ＤＨＴ干预组Ｍｕｃ１、Ｍｕｃ４ｍＲＮＡ表达水平较空白对照组明显增加,差异均有统计学意义（均为Ｐ＜０．０５）;０．０５ｇ?Ｌ－１、０．２０ｇ?Ｌ－１、０．５０ｇ?Ｌ－１ＤＨＴ干预组表达均下降,差异均有统计学意义（均为Ｐ＜０．０５）。免疫荧光化学检测结果示,以上各组Ｍｕｃ１ＯＤ值分别为１．８６±０．０１、１．８２±０．０１、２．０３±０．０４、１．８８±０．０１、１．８１±０．０２,０．１０ｇ?Ｌ－１ＤＨＴ干预组Ｍｕｃ１表达较空白对照组明显增加,０．０５ｇ?Ｌ－１、０．５０ｇ?Ｌ－１ＤＨＴ干预组表达均下调,差异均有统计学意义（均为Ｐ＜０．０５）;Ｍｕｃ４ＯＤ值分别为１．８６±０．００、１．７７±０．０１、１．８４±０．０２、１．９２±０．００、１．６９±０．０５,０．１０ｇ?Ｌ－１与０．２０ｇ?Ｌ－１ＤＨＴ干预组Ｍｕｃ４表达较空白对照组明显增加,０．０５ｇ?Ｌ－１、０．２０ｇ?Ｌ－１、０．５０ｇ?Ｌ－１ＤＨＴ干预组表达均下调,差异均有统计学意义（均为Ｐ＜０．０５）。０．５０ｇ?Ｌ－１与１．００ｇ?Ｌ－１ＤＨＴ可影响细胞体外生长。结论　一定浓度ＤＨＴ（如０．１０ｇ?Ｌ－１）可上调小鼠角膜上皮细胞Ｍｕｃ１与Ｍｕｃ４的表达水平;而高浓度（０．５０ｇ?Ｌ－１与１．００ｇ?Ｌ－１）ＤＨＴ对角膜上皮细胞存在毒性作用。     

Interactions of testosterone and all-trans retinoic acid in regulation of androgen receptor expression in rat lacrimal gland

All-trans retinoic acid down-regulates androgen receptor (AR) expression in lacrimal gland acinar cells in culture. The goal of this study was to determine if retinoic acid inhibits androgen-stimulated up-regulation of AR protein and AR mRNA expression in lacrimal glands of orchiectomized rats in vivo. Delivery of androgens to orchiectomized rats was accomplished by subcutaneous implantation of a 25 or 50 mg 21-day slow-release testosterone pellet. Rats were treated with retinoic acid by gastric gavage at 20 mg kg(-1) day(-1). After 7 days of treatment lacrimal glands were removed, AR protein expression in frozen sections was determined by immunohistochemistry and total RNA was probed for AR mRNA expression. Serum testosterone was measured by ELISA and serum retinoic acid was detected by HPLC. Orchiectomy decreases serum testosterone to 17 +/- 8 ng dl(-1), compared to 143 +/- 27 ng dl(-1) in normal rats, and reduces the number of lacrimal acinar cell nuclei expressing ARs to less than 30% of normal. Implantation of testosterone pellets restored lacrimal AR expression, but increased serum testosterone to more than 10 times the normal levels. Retinoic acid failed to inhibit AR expression in rats with high serum testosterone. Therefore a dose-response study was conducted in which testosterone was delivered by injection of a single dose of Depotestosterone at 2.5-200 mg kg(-1). Treatment of orchiectomized rats with a dose of testosterone as low as 2.5 mg kg(-1) resulted in serum testosterone levels of 62 +/- 17 ng dl(-1) and significantly increased lacrimal gland AR expression. Delivery of retinoic acid at 20 or 50 mg kg(-1) day(-1) simultaneously with a 2.5 mg kg(-1) testosterone injection prevented restoration of lacrimal gland AR expression and significantly reduced AR mRNA expression. A pharmacologic dose of retinoic acid inhibits AR expression in lacrimal gland acinar cells in vivo, as well as in vitro. This indicates that effects of retinoic acid and testosterone are antagonistic and suggests that retinoic acid may modulate effects of testosterone on the lacrimal gland.     

Intravitreally injected ranibizumab versus photodynamic therapy for CNV secondary to choroidal osteoma: a 7-year follow-up case report

Meibomian gland, the largest sebaceous gland of the body, is responsible for the biosynthesis of lipid layer of the tear film to prevent excessive evaporation. The loss of normal functions of meibomian gland, known as meibomian gland dysfunction (MGD), is a chronic disease and is the leading cause of dry eye symptoms in the clinics. Studies have found sex hormones, especially androgen, play vital roles in the regulation of the functions of meibomian gland. Recently, androgen has also been preliminarily applied in clinics for the treatment of MGD and showed promising results, especially in people with endogenous androgen deficiency. This review summarized the mechanisms of the function of androgen on meibomian gland based on molecular, animal, and clinical studies, and propose evidence-based views about its potential applications for the treatment of MGD.     

性激素在圆锥角膜中的作用及潜在治疗靶点

圆锥角膜是一种青春期起病，以角膜中央或旁中央变薄呈锥形突出为特征的致盲性眼病。目前该病的病因尚不明确，研究发现其发生与遗传、揉眼、变态反应性疾病、紫外线照射均有一定的相关性。近年来，多项研究表明性激素在圆锥角膜发病过程中也有一定影响，体内性激素的紊乱可增加圆锥角膜的发生及进展风险。本综述旨在总结性激素对角膜的病理生理作用，明确其对圆锥角膜的影响及其相关炎症和免疫机制，探求其在圆锥角膜早期诊疗中的作用，以期为临床工作提供参考及帮助。     

Effects of extract of Buddleja officinalis on partial inflammation of lacrimal gland in castrated rabbits with dry eye

AIM: To assess the effects of extract of Buddleja officinalis on tear secretion volume, tear film stability, expressions of TGF-β1, IL-1β, TNF-α in lacrimal gland of castrated rabbits with dry eye. METHODS: A total of 30 victory rabbits were divided averagely into normal group(A), model group(B), therapy group with low dose extract of Buddleja officinalis (C), therapy group with high dose extract of Buddleja officinalis (D) and therapy group with genistein (E). The dry eye model was established with orchiectomy on Group B, C, D, E. Group C, D, E were administered intragastrically with corresponding dose extract of Buddleja officinalis or genistein for 30 days. All rabbits were detected with SIT. TGF-β1, IL-1β, TNF-α were detected with immunohistochemistry and the ultrastructure of lacrimal gland was observed under transmission electron microscope. RESULTS: The SIT value of group C, D, E were respectively 13.167±4.957, 14.667±5.279, 8.667±0.516, obviously higher than that of group B 5.667±2.338 (P<0.01). The positive expression of IL-1β in acinar cell and glandular tube cell of group C, D were 0.470±0.048, 0.510±0.088, obviously lower than that of group B 0.770±0.118 (P<0.01). The positive expression of TNF-α of group C, D were 0.498±0.156, 0.435±0.069, obviously lower than that of group B 0.769±0.095 too (P<0.01). The positive expression of TGF-β1 of group C, D were 0.406±0.171, 0.497±0.147, obviously higher than that of group B 0.222±0.113(P<0.01). Any result of group C, D was positive compared with that of group E (P <0.05). Ultrastructure of the lacrimal gland of group C, D, E was well preserved, especially in D group it was remarkable. CONCLUSION: The extract of Buddleja officinalis can adjust lacrimal gland partial inflammation of dry eye.     

雌雄激素对去卵巢雌鼠泪腺TGF-β1表达的影响

目的探讨雌雄激素对去卵巢雌鼠泪腺中TGF-β1表达的影响。方法3个月龄雌性Wistar大鼠64只,随机分为正常对照组8只、假手术组8只、实验组48只。实验组行双侧卵巢切除术（OVX）。分别于术前及术后第1、2、3、4、5个月行泪液分泌量（Schirmer试验）、泪膜破裂时间（BUT）检查。于术后5个月将实验组按随机数字表法分组,分别全身及局部给予玉米油、苯甲酸雌二醇、丙酸睾丸酮,观察给药6周后Schirmer试验、BUT结果,并取其泪腺检测TGF-β1的浓度。结果OVX术后5个月大鼠血清雌二醇水平及睾酮水平均降低（P〈0．05）。术后1个月BUT较术前缩短（P〈0．01）;术后3个月Schirmer试验结果较术前缩短50％（P〈0．01）。全身雌激素治疗6周后BUT缩短（P〈0．01）;Schirmer试验结果缩短（P〈0．05）。全身雄激素治疗6周后BUT延长（P〈0．05）,Schirmer试验结果延长（P〈0．05）;泪腺中TGF-β1浓度为（20．24±3．99）pmol／L,较空白对照组（6．23±1．09）pmol／L升高（P〈0．01）。结论雄激素促进去卵巢雌鼠泪液分泌及泪腺中TGF-β1的表达。     

蒸发过强型干眼诱发因素研究进展

干眼主要分为水样液缺乏型干眼和蒸发过强型干眼。蒸发过强型干眼是在泪液分泌功能正常的情况下,由各种因素导致暴露的眼球表面泪液过量损失引起的。诱发此类干眼的因素包括泪膜脂质层异常、瞬目频率降低、配戴角膜接触镜、眼表障碍及眼表疾病、环境因素等。随着信息社会的发展,人们生活和工作方式的改变,蒸发过强型干眼的发病率逐渐增高,发病年龄年轻化,而临床上蒸发过强型干眼容易被忽视或误诊,就其主要诱发因素及其诊断和治疗的研究进展进行综述。