染矽尘大鼠肺匀浆TGF-β1和TNF-α的变化

目的探讨染矽尘大鼠肺匀浆TGF-β1和TNF-α的变化.方法采用一次性气管内注入矽尘方法建立动物模型.称量法测定脏器系数,过氧化氢方法测定胶原含量.采用ELISA测定肺匀浆TGF-β1和TNF-α蛋白浓度.结果实验过程中,实验组TGF-β1在染尘后第7天显著低于对照组(P＜0.01),而第14天显著高于对照组(P＜0.05),其他时点,差异无显著性.TNF-α在染矽尘后第14天显著升高(P＜0.05),而在14 d后显著性降低(P＜0.01).TGF-β1与肺胶原含量呈显著相关(r=0.435,P=0.009),而TNF-α与肺胶原含量之间无相关(r=0.108,P＞0.05).结论矽尘可导致大鼠肺TGF-β1和TNF-α的变化,TGF-β1可能介导矽肺的肺胶原合成.     

染矽尘大鼠早期肺组织肿瘤坏死因子的表达

目的采用组织芯片和图像分析技术阐述染矽尘大鼠早期肺组织炎性损伤过程中肿瘤坏死因子-α(TNFα)表达的变化规律。方法采用气管暴露法建立矽肺动物模型。免疫组织化学链霉菌抗生物素蛋白-过氧化物酶法(SP)结合组织芯片技术检测肺组织TNFα的表达。用ImageProPlusVersion4.5forWindowsTM图像分析系统对TNFα的表达做定量分析。结果染矽尘组TNFα阳性细胞面积百分比于染尘后第3天时开始升高,一直持续到第14天,第21天后稍有回落。第7天时达高峰,染矽尘组阳性面积百分比较对照组高出6.57,差异有显著性(P<0.01)。结论矽尘可诱导大鼠肺组织炎性损伤早期TNFα的过度表达。     

烟酸对染矽尘大鼠肺组织Ⅰ型和Ⅲ型胶原形成的影响

目的 阐明饲料中添加烟酸对染矽尘大鼠早期Ⅰ型、Ⅲ型胶原形成的影响。方法 采用气管暴露法建立矽肺动物模型,高效液相色谱法测定血浆烟酸含量,天狼红染色法结合偏振光显微镜观察Ⅰ型、Ⅲ型胶原的形成,图像分析系统对胶原定量分析。结果 烟酸组不同时点血浆中烟酸含量明显升高,与对照组和矽尘组相比,差异均有显著性。染矽尘后第7天、第28天,与对照组比较,矽尘组大鼠肺组织Ⅰ型胶原阳性区域面积百分比显著增加,而烟酸组Ⅰ型胶原阳性区域面积百分比则明显低于矽尘组。染矽尘后第28天,Ⅲ型胶原阳性区域面积百分比显著高于对照组,而烟酸组Ⅲ型胶原阳性区域面积百分比则显著低于矽尘组。结论烟酸通过抑制Ⅰ型、Ⅲ型胶原的形成,而有效地阻断矽尘诱导的大鼠肺纤维化。     

川芎嗪对染矽尘大鼠肺组织Ⅰ、Ⅲ型胶原合成的影响

目的观察川芎嗪对染矽尘大鼠肺组织Ⅰ、Ⅲ型胶原合成的影响。方法将大鼠随机分为对照组、染矽尘组、川芎嗪组,采用一次性气管内注入矽尘法建立矽肺动物模型,川芎嗪组每日腹腔注射川芎嗪注射液50mg/kg。染尘后按不同时间点取大鼠肺组织制作石蜡切片,采用天狼猩红染色结合偏振光显微镜观察Ⅰ、Ⅲ型胶原的表达,ImageProPlus图像分析系统进行定量分析。结果染矽尘后第3天,Ⅲ型胶原开始增生,染矽尘后第7天,Ⅰ型胶原开始增生,直至染矽尘后第28天,这两种胶原进行性增加。与对照组相比,各时间点染矽尘组大鼠肺组织Ⅰ、Ⅲ型胶原面积百分比均有不同程度增加,而川芎嗪组Ⅰ型胶原面积百分比在第7、14、28天,Ⅲ型胶原面积百分比在第28天时明显低于染矽尘组。结论矽尘可以诱导大鼠肺组织Ⅰ、Ⅲ型胶原合成增加,两型胶原出现增生的时相有所不同;川芎嗪可以抑制矽尘诱导的Ⅰ、Ⅲ型胶原的合成。     

染矽尘小鼠肺组织中转化生长因子β1表达的逆转录聚合酶链反应检测

目的　探讨染矽尘小鼠肺组织转化生长因子 β1(TGF β1)基因的表达在矽肺发病中的意义。方法　采用暴露式气管内注入法给小鼠一次性染矽尘 (0 .2g/kg体重 ) ,染尘后第 1、3、5、7、14、2 8天 ,每组各处死 8只小鼠 ,取肺组织 ,用逆转录聚合酶链式反应 (RT PCR)方法测定小鼠肺组织TGF β1基因的表达。结果　染尘后第 3天 ,小鼠肺组织中TGF β1基因表达开始升高 (1.2 0± 0 .15 ) ;第 7天达高峰 (1.74± 0 .19) ,与对照组 (1.0 1± 0 .16 )和染尘第 5天 (1.35± 0 .15 )比较 ,差异均有显著性 (P <0 .0 5 ) ;第 14天开始下降 ,但直到第 2 8天仍高于对照组。染矽尘小鼠肺组织羟脯氨酸含量随染毒后时间的延长 (1～ 2 8d)呈现持续上升的趋势。结论　TGF β1在矽肺早期的发生、发展过程中可能有重要作用。     

染矽尘大鼠血硅及尿硅含量与肺纤维化程度的关系

目的探讨染矽尘大鼠血、尿中硅含量与肺组织中羟脯氨酸、Ⅰ型胶原、Ⅲ型胶原含量的关系。方法处理组采用气管灌注法注入矽尘混悬液建立大鼠矽肺模型,对照组采用同样处理但用生理盐水代替矽尘混悬液。两组取第28天大鼠的血液、尿液,经样品前处理后用原子吸收分光光度计检测;大鼠肺组织制作石蜡切片,采用天狼猩红染色法,用偏振光显微镜和图像分析系统对肺组织Ⅰ型胶原、Ⅲ型胶原的表达进行分析;试剂盒检测肺组织羟脯氨酸含量。结果处理组大鼠血硅、尿硅、Ⅰ型胶原及Ⅲ型胶原明显高于对照组(P<0.05),羟脯氨酸虽稍低于对照组,但无统计学意义(P>0.05);血硅、尿硅分别与Ⅰ型胶原、Ⅲ型胶原建立直线回归,有统计学意义(P<0.05),血硅、尿硅分别与羟脯氨酸建立直线回归,无统计学意义(P>0.05)。结论血硅、尿硅对早期矽肺纤维化程度可能有一定的指示意义。 更多还原     

牛磺酸对染矽尘大鼠肺组织炎性细胞影响

目的 探讨牛磺酸对染矽尘大鼠肺组织炎性细胞趋化的影响.方法 Wistar大鼠144只,随机分为对照组、染矽尘组和牛磺酸组,后2组气管内注入质量浓度为50 g/L的矽尘混悬液,牛磺酸组在实验开始前3d即给予含质量分数为2.5％的牛磺酸饲料持续喂养,对照组气管内注入等体积灭菌生理氯化钠溶液.偏振光显微镜观察肺纤维化发生情况,行在体全肺灌洗术,血细胞计数仪测定支气管肺泡灌洗液细胞数.结果 牛磺酸组第7、14、21和28天炎性细胞总数均低于染矽尘组,差异有统计学意义(P＜0.05).牛磺酸组第14、21天巨噬细胞数低于染矽尘组,差异有统计学意义(P＜0.05).牛磺酸组第21天中性粒细胞数低于染矽尘组,差异有统计学意义(P＜0.05).牛磺酸组第14、21天淋巴细胞数均低于染矽尘组,差异有统计学意义(P＜0.05).结论 牛磺酸对矽尘诱导大鼠肺组织巨噬细胞、中性粒细胞、淋巴细胞的趋化具有抑制作用.     

牛磺酸对染矽尘大鼠肺组织Ⅰ和Ⅲ型胶原合成及比例的影响

目的 探讨牛磺酸对染矽尘大鼠肺组织不同时相Ⅰ、Ⅲ型胶原合成及比例的影响.方法 将Wistar大鼠144只随机分为对照组（生理盐水,普饲）、矽肺组（普饲）和牛磺酸组（牛磺酸饲料）给予气管内注入1 ml矽尘混悬液（50 mg/ml）,每组48只.分别在第1、3、7、14、21、28天时,用高效液相色谱法测定其血浆中牛磺酸含量;取肺组织制作石蜡切片,天狼猩红法染色,偏振光显微镜观察各组动物肺组织Ⅰ、Ⅲ型胶原的合成及比例的变化,图像分析系统对其进行定量分析.结果 第7、14、21和28天,矽尘组Ⅰ型胶原含量分别比对照组增加3.84%、3.77%、3.73%、9.83%,差异有统计学意义（P＜0.01）.第7、21和28天时,牛磺酸组Ⅰ型胶原含量分别比矽尘组降低2.39%、1.62%和7.13%;与对照组比较,第14、21和28天Ⅰ型胶原含量分别增加2.12%、2.11%和2.70%,差异均有统计学意义（P＜0.05或P＜0.01）.第28天时,牛磺酸组Ⅲ型胶原含量比矽尘组减少2.62%,差异有统计学意义（P＜0.05）.矽尘组Ⅰ/Ⅲ型胶原比例第7天开始增加,第28天时达到最大比值1.87,牛磺酸组Ⅰ/Ⅲ型胶原比例从第7天开始增加,且增加幅度高于矽尘组,第28天时增加幅度低于矽尘组.结论 牛磺酸对矽尘诱导大鼠肺组织不同时相的Ⅰ、Ⅲ型胶原合成抑制作用不同.     

染矽尘大鼠肺组织不同时间点FasL表达与细胞凋亡

目的探讨染矽尘大鼠肺组织FasL表达及细胞凋亡在矽肺病理变化中的意义。方法将96只Wistar大鼠随机分为对照组和染矽尘组。对染矽尘组以暴露式气管内一次注入二氧化硅粉尘悬液(1 ml,0．2 g/kg)建立大鼠矽肺模型,对照组气管内注入1 ml灭菌生理盐水。分别于处理后1、3、7、14、21和28 d,每组分别取8只大鼠处死取肺组织,用组织芯片技术结合免疫组化SP法检测大鼠肺组织不同时间点FasL的表达;末端脱氨核苷酸转移酶末端标记技术(TUNEL)法检测大鼠肺组织细胞凋亡,并采用Image-Pro Plus Version 4．5 for windowsTM图像分析计算积分光密度。结果染矽尘组大鼠肺组织FasL在染矽尘后的7、14、21和28 d时,表达明显高于对照组,差异有统计学意义(P<0．05),14 d时表达最高为157．50±23．12;染矽尘组大鼠肺组织凋亡阳性细胞在染矽尘后的1、3、7、14、21和28 d时,明显高于对照组,差异有统计学意义(P<0．05),7和14d,分别最高为32．95±20．40和31．07±7．15。结论矽尘能导致肺组织细胞凋亡;FasL在染矽尘大鼠肺组织多种细胞中表达并介导细胞的凋亡,凋亡细胞主要以炎性细胞为主。     

我国矽肺治疗的现况

矽尘与肺泡巨噬细胞之间相互作用是矽肺发病的关键;矽尘破坏巨噬细胞生物膜是矽肺发病的起点;巨噬细胞释放的多种因子是形成矽肺的必要条件。矽肺治疗,旨在加速清除肺内的矽尘,降低矽尘的细胞毒性,保护肺泡巨噬细胞,阻断胶原形成,分解矽性病灶中的胶原蛋白、脂蛋白和多脂。关于治疗矽肺的药物,20多年来我国劳     

肺癌病因研究中接尘量计算的真实性评价

为评价肺癌病例对照研究中接尘剂量估算方法的真实性,对广西锡矿病因研究对象进行了重新计算。广西锡矿队列发现男性肺癌死者１３０例,配对照６２７例。共７５７人。其中接法工人５７２名,发现各期矽肺共２４３例,根据在斩工业卫生监测资料估算所有接尘工人的累积总粉尘接触量,再计算不同接尘水平下矽肺的发病率。结果显示,随接尘水平上升,矽肺发病率升高,两者存在明显的接触剂量反应关系。完全符合矽肺发病特点。从而间接证     

二氧化硅对大鼠血浆中微量元素含量的影响

给大鼠经气管分别注入４、１６、６４ｍｇ石英粉尘生理盐水混悬液。在染尘后第７，１５和３０天解剖动物，测定血浆中Ｃｕ、Ｚｎ，Ｍｎ、Ｍｏ、Ｓｉ、Ｒｂ和Ｓｒ等７种微量元素的含量。实验结果表明，随着染尘剂量的增加，血浆中铜的含量明显增高，呈正相关，相关系数为０．９９９。而血浆锌的含量随着染尘剂量的增加而明显的降低，呈负相关，相关系数为－０．９９８。血浆中Ｍｏ、Ｍｎ、Ｓｉ、Ｒｂ和Ｓｒ含量与对照组比无明显差异。     

铀矿尘致大鼠肺纤维化过程中Ⅰ和Ⅲ型胶原及层粘连蛋白表达的变化

目的 探讨铀矿尘致大鼠纤维化过程中Ⅰ、Ⅲ型胶原、层粘连蛋白(Laminin,LN)表达的变化特征.方法 60只Wistar大鼠随机分为铀矿尘组(30只)和对照组(30只),铀矿尘组大鼠一次性非暴露气管内滴注20 mg/ml的粉尘悬液1 ml,对照组大鼠一次性气管内滴注生理盐水1 ml,分别于处理后7、14、21、30及60 d每组随机处死6只,取肺组织,HE染色观察肺组织形态学改变,天狼猩红染色法观察肺组织Ⅰ、Ⅲ型胶原变化,免疫组织化学法检测LN蛋白的表达.结果 铀矿尘致肺组织纤维化过程中可见Ⅰ、Ⅲ型胶原的大量增生,染尘后早期主要以Ⅰ型胶原增生为主.铀矿尘组21、30、60d时Ⅰ型、Ⅲ型胶原纤维面积百分比明显增高,与对照组比较,差异均有统计学意义(P＜0.05或P＜0.01).LN主要见于肺组织内血管、支气管周围、血窦壁以及肺间隔的基底膜,形态上以增粗的线状或丛状分布为主.铀矿尘组21、30、60 d时肺组织中LN阳性细胞积分吸光度(14.89±2.25、22.98±2.29、30.34±2.19)增加,与对照组(9.06±1.21、8.98±0.86、10.04±2.00)比较,差异有统计学意义(P＜0.05,P＜0.01).结论 铀矿尘诱导大鼠肺组织纤维化早期以Ⅰ型胶原纤维为主,后期Ⅰ型、Ⅲ型胶原纤维均大量增多,分布范围扩大.肺组织过程中有LN高表达.

Abstract：

Objective To explore the characteristics of LN and type Ⅰ, Ⅲ collagen in pulmonary fibrosis induced by uranium ore dust in rats. Methods 60 adult Wistar rats were divided randomly into two groups, control group (30 rats)and uranium ore dust group (30 rats). Non-exposed intratracheal instillation method was used. Uranium ore dust group was exposed 20 mg/ml uranium ore dust suspension 1ml per rat,meanwhile control group was exposed normal saline 1ml per rat. Post-exposed the 7, 14, 21, 30 and 60 d, 6 rats in each group were killed randomly, lung tissue were collected. The pathological changes in lung tissue were observed by microscope using HE staining, the collagen Ⅰ and Ⅲ in lungs were observed by polarizing microscope using Biebrich scarlet staining. The expression of LN protein in lung tissue was observed by immunohistochemistry-SP. Results During lung fibrosis, a large amount of the proliferated Ⅰ and Ⅲ collagen in lungs were observed. Post-exposure to uranium ore dust, the characteristics in proliferated collagen in lungs were type Ⅰ collagen deposited in lung interstitium mainly in the early stage. The area percentage of collagen Ⅰ and Ⅲ was increased significantly at 7,14, 21, 30 and 60 d in the experimental group as compared with that in the control group (P＜0.05 or P＜0.01). The over expression of LN in the lung tissue were observed. The expression of LN was distributed in the lung tissue as thickening of the linear or cluster. The integral optical density of LN was increased significantly at 21,30 and 60d in the experimental group as compared with that in the control group(P＜0.05 or P＜0.01). Conclusions After exposure to uranium ore dust, the characteristics in proliferated collagen in lungs are the type of Ⅰ collagen deposited in lung interstitium mainly in the early stage, while the type of Ⅲ collagen increase significantly at the later period. The overexpression of LN exists in the process of pulmonary fibrosis. It suggests that LN has a role effect in the process of pulmonary fibrosis.     

早期联合用药对矽尘致大鼠肺纤维化的影响

目的：探讨早期用药对矽尘致大鼠肺纤维化的影响。方法采用ＳＤ大鼠,低剂量石英寺非暴露式气管注入染尘（２０ｍｇ／鼠）后３ｄ,在病变早期阶段开始给药,分别治疗２个月和５个月。疗效指标为肺湿重、肺胶元含量、肺总脂含量及肺内矽性病变分级。结果：以肺湿重、肺总脂为依据的综合疗效指标显示,各用药组都显著低于染尘对照组。肺内矽性病变分级亦有相应的差异。结论：早期联合用药对大鼠肺纤维化有一定阻断作用,其疗效优于各单     

Case-control study of silicosis, silica exposure, and lung cancer in white South African gold miners

A case-control study was undertaken to assess the association between lung cancer and silicosis or silica dust exposure in white South African gold miners. Cases and controls were identified from deaths reported to the Gold Miners Provident Fund for the period January, 1979-October, 1983. Two controls were matched to each case by year of birth (+/- 2 years) and by smoking (+/- 5 cigarettes or equivalents per day) assessed 10 years (+/- 2 years) prior to death. One hundred thirty-three matched triplets were identified. The results showed no overall association between lung cancer and radiological silicosis (OR = 1.08, p = 0.92). Autopsy data indicated no overall associations between lung cancer and silicosis of the lung parenchyma (OR = 1.49, p = 0.11), the pleura (OR = 0.72, p = 0.30), or the hilar glands (OR = 0.85, p = 0.72). A trend toward increased severity of silicosis of the parenchyma was evident; however, this was not statistically significant (p = 0.08). Odds ratios for lung cancer and silicosis were higher at lower levels of cumulative silica dust exposure (ORs = 2.43, 1.72, 1.35 and 0.62 for lung cancer and autopsy silicosis of the parenchyma for the lowest, second, third, and highest quartiles of dust exposure, respectively; all p greater than 0.05). Cases did not differ from controls for total silica dust exposure, length of exposure, weighted average intensity of exposure, or number of shifts at high dust (all p greater than 0.20). The data do not support the hypothesis of a carcinogenic role for silica dust and no statistically significant associations were found between lung cancer and silicosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

大鼠染矽尘后不同时间重复移植人脐带间充质干细胞对肺纤维化的影响

目的 探讨人脐带间充质干细胞（human umbilical cord mesenchymal stem cells,HUCMSCs）在不同时间窗的重复移植对染矽尘大鼠肺纤维化的疗效。
方法 将48只健康雄性SD大鼠随机分为4组:对照组、矽肺模型组、预防性干预组和治疗性干预组（每组12只）。采用非暴露式气管插管内灌注法,对照组注入0.5 mL生理盐水,其余各组均注入0.5 mL二氧化硅（SiO₂）混悬液（50 mg/mL）,1周后重复1次。首次染尘后,预防性干预组在第1、7、14、21天,治疗性干预组在第28、35、42、49天,经尾静脉缓慢注射0.5 mL HUCMSCs细胞悬液（3.0×109/L）。在第70天统一处理动物,以HE染色和Masson染色,观察肺组织病理改变并进行Aschcroft肺纤维化评分,检测肺系数、肺组织羟脯氨酸（hydroxyproline,Hyp）及转化生长因子-β₁（TGF-β₁）、血清白细胞介素-6（IL-6）的水平。
结果 肺组织病理显示,对照组肺泡结构正常,其余各组肺脏有不同程度纤维化病变,矽肺模型组见细胞纤维性肉芽肿形成,预防性干预组和治疗性干预组与矽肺模型组比较,胶原纤维明显减少;Aschcroft评分、肺系数、肺组织Hyp和TGF-β₁、血清IL-6比较,染尘各组均明显高于对照组（P < 0.01）,而预防性干预组和治疗性干预组明显低于矽肺模型组（P < 0.01）,预防性干预组和治疗性干预组之间以上指标差异均无统计学意义（P>0.05）。
结论 采用重复注射HUCMSCs的方法,无论在以肺泡炎为主的阶段还是在以纤维化为主的阶段进行干预,均可以有效减轻矽尘导致的大鼠肺纤维化。
     

A case-referent study investigating the relationship between exposure to silica dust and lung cancer

Summary A case-referent study was carried out to investigate the relationship between lung cancer and exposure to silica dust in an area where a relatively high proportion of the workforce was exposed to silica dust in the past. The cases were 309 lung cancer patients admitted at the Chest Department of the Central Belluno Hospital during the period 1973–1980, while the 309 controls were patients admitted at the same department for diseases other than lung cancer and bronchitis during the same period. Information on exposure to silica and smoking habits were collected from hospital records. The results show an elevated risk, supported by a clear dose-response, due to smoking. Exposure to silica also appears to increase the risk of lung cancer, but only in presence of silicosis. The risk estimates tend to increase both with amount of smoking and duration of exposure to silica, with the magnitude of the risk being, however, much smaller for the latter effect. No clear interaction appears to exist between the two factors. The limitations of the study and the problems in interpreting the results are discussed.     

Early Changes in the Chemical Composition of the Rat Lung after Silica Administration

A group of 200 g male Sprague-Dawley rats was injected with 75 mg of quartz (< 5 μ particle size) and changes in lung DNA, noncollagenous protein, total lipids, and collagen were studied after 6 , 24, 72, 96, and 144 hr. Another group of rats received 10, 30, 59, and 75 mg quartz and the above lung analysis was performed 6 days later. Control rats received saline only. Both sets of experiments indicate that striking changes in the above parameters occur very early. The sequence of statistically significant changes was: lung weight (24 hr), DNA (24 hr), noncollagenous proteins (72 hr), total lipids (72 hr), collagen (144 hr). At the dose of 30 mg quartz/lung all the above parameters were significantly increased within 6 days after the lung injury. It is proposed that in early stages of experimental silicosis an excessive amount of collagen accumulates in the lung. Later, some of the deposited collagen is resorbed. This indicates that in the course of the silicotic fibroproliferative inflammation, the balance between collagen deposition and degradation varies.     

两种矽肺造模方法比较

目的 比较两种矽肺造模方法的优劣,并探讨一次性气管滴注法造模的最佳时间。方法 口鼻暴露染尘小鼠20只,气管滴注染尘小鼠20只,分别于染尘后第7、14、21、28天处死;对照组小鼠5只,正常饲养28d处死。检测各时间节点小鼠肺湿重、脏器系数、肺组织羟脯氨酸(hydroxyproline,HYP)含量,并观察肺组织病理改变。结果 口鼻暴露法染尘21、28d小鼠肺湿重及脏器系数,7、14、21、28d小鼠肺纤维化评分,与对照组比较差异有统计学意义(P<0.05),染尘28d小鼠肺组织形成矽结节;气管滴注染尘后第14、21、28天小鼠肺湿重、脏器系数,第28天小鼠HYP含量,第7、14、21、28天小鼠肺纤维化评分,与对照组比较差异有统计学意义(P<0.05),染尘后第21天形成多个矽结节,第28天矽结节融合成大片状。结论 暴露法染尘28d小鼠开始形成矽结节,滴注法染尘后第21天小鼠即可完成矽肺造模。     

矽肺大鼠和病人肺组织中Ⅰ型与Ⅲ型胶原纤维的分布及相对含量的研究

免疫酶标法用于观察肺组织中胶原的分布。显微分光光度法用于研究大鼠与矽肺病人的纤维化组织中Ⅰ型与Ⅲ型胶原的相对含量。染色中应用大鼠及人的抗Ⅰ型与Ⅲ型胶原多克隆抗体。Ⅰ型胶原分布于正常肺泡间隔及间质中。Ⅲ型胶原也在相同的部位存在。在由石英所致的大鼠纤维化肺组织中,Ⅰ型与Ⅲ型胶原在极度扩展的间质中聚集。Ⅲ型胶原是早期纤维化肺中主要增生的胶原。Ⅰ型胶原是纤维化后期主要增生的胶原。在矽肺病人肺组织中也见到同样的现象。染电焊烟尘的大鼠肺,直至180天以前,Ⅲ型胶原为主要积聚的胶原,而在180天以后,Ⅰ型胶原的增加才占优势。