Zhai Rui-xue, Yao Lin, Yao Xue, Yan Li-cheng, Hao Yu-lan, Guan Wei-jun, Zhang Jun, Zhang Yan-shu
Department of Toxicology, School of Public Health, Hebei United University, Tangshan, Hebei Province 063000, China.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2012 Sep;30(9):667-71.
To investigate the change of lung surfactant protein (SP) A,B,C,D of rats following silica dust exposure in order to provide the evidences for the early diagnosis indices or therapy of silicosis.
60 male SD rats were randomly divided into silica group, and corresponding controls group. Rats in silica group were administrated 1 ml silica solution by intratracheal instillation at dose of 50 mg/ml. Rats in control group were administrated the same amount saline. At 3rd, 7th, 14th, 21st, 28th after silica exposure, serum and bronchoalveolar lavage fluid (BALF) samples were obtained. The concentration of SP-A, SP-B, SP-C, SP-D in serum and BALF were measured by using enzyme immunoassay (ELISA). Meanwhile the levels of total anti-oxidative activity (T-AOC) and hydroxyproline (HYP) in lung tissue were also detected. The pathology of lung tissue was conducted.
Compared with control group, SP-A concentration in BALF of silica exposed rat for 3, 14, 21, 28d was significant lower and SP-D concentration in BALF of silica exposed rat for all time points was also lower. The differences were significant (P < 0.05). Meanwhile SP-B level in 7, 14, 21, 28 d silica exposed rats BALF and SP-C level in 14, 21, 28 d silica exposed rats markedly decreased (P < 0.05). In addition compared with control group, SP-A, SP-B and SP-C concentration in serum of silica exposed rat were higher when SP-A for 14, 21, 28 d silica exposure, SP-B for 7, 14, 21 d silica exposure and Sp-C for 7, 14, 21, 28 d exposure. And all difference were significant (P < 0.05). As silica exposure time increased, SP-C concentration in serum showed an increase trend, which showed a time-response relationship (r = 0.618, P = 0.042). However, SP-D concentration in serum of rat for 7, 14, 21, 28d silica exposure were significant lower than that of control group (P < 0.005). And there was a decrease trend with time point exposure regarding of SP-D (r = -0.731, P = 0.016). The HYP content in lung tissue of experiment rats increased at 3rd, 7th, 14th, 21st and 28th day time point and The T-AOC activity in lung tissue decrease at, 7th, 14th, 21st and 28th day time point. The differences were significant (P < 0.05). There was a positive correlation (P = 0.803, P = 0.045) between SP-C in BALF and HYP of silica exposed rats and a negative correlation between SP-D in BALF and HYP (r = -0.867, P = 0.033). No significant correlation were seen between SP-A, SP-B BALF and HYP (y = 0.416, P = 0.28; r = 0.592, P = 0.071). SP-C concentration in BALF and serum all showed an increased trend and a positive correlation was seen (r = 0.539, P = 0.046). The same decrease trend was seen between SP-D in BALF and serum and correlation value was 0.870 (P = 0.034).
The silica exposure did cause the change of SP content both in BALF and serum. The SP-C and SP-D content in serum might be served as an early effective biomarker of silicosis.
探讨二氧化硅粉尘暴露后大鼠肺表面活性蛋白(SP)A、B、C、D的变化,为矽肺的早期诊断指标或治疗提供依据。
将60只雄性SD大鼠随机分为二氧化硅组和相应的对照组。二氧化硅组大鼠经气管内滴注1 ml浓度为50 mg/ml的二氧化硅溶液。对照组大鼠给予等量生理盐水。在二氧化硅暴露后第3、7、14、21、28天,采集血清和支气管肺泡灌洗液(BALF)样本。采用酶联免疫吸附测定(ELISA)法检测血清和BALF中SP-A、SP-B、SP-C、SP-D的浓度。同时检测肺组织中总抗氧化活性(T-AOC)和羟脯氨酸(HYP)水平。进行肺组织病理学检查。
与对照组相比,二氧化硅暴露3、14、21、28天大鼠BALF中SP-A浓度显著降低,各时间点二氧化硅暴露大鼠BALF中SP-D浓度也降低。差异有统计学意义(P<0.05)。同时,二氧化硅暴露7、14、21、28天大鼠BALF中SP-B水平及14、21、28天大鼠BALF中SP-C水平明显降低(P<0.05)。此外,与对照组相比,二氧化硅暴露大鼠血清中SP-A、SP-B和SP-C浓度在二氧化硅暴露14、21、28天的SP-A、7、14、21天的SP-B和7、14、21、28天的SP-C时较高。且差异均有统计学意义(P<0.05)。随着二氧化硅暴露时间增加,血清中SP-C浓度呈上升趋势,呈现时间-反应关系(r=0.618,P=0.042)。然而,二氧化硅暴露7、14、21、28天大鼠血清中SP-D浓度显著低于对照组(P<0.005)。且SP-D随时间点暴露呈下降趋势(r=-0.731,P=0.016)。实验大鼠肺组织中HYP含量在第3、7、14、21和28天时间点增加,肺组织中T-AOC活性在第7、14、21和28天时间点降低。差异有统计学意义(P<0.05)。二氧化硅暴露大鼠BALF中SP-C与HYP呈正相关(P=0.803,P=0.045),BALF中SP-D与HYP呈负相关(r=-0.867,P=0.033)。SP-A、SP-B BALF与HYP之间未见明显相关性(y=0.416,P=0.28;r=0.592,P=0.071)。BALF和血清中SP-C浓度均呈上升趋势且呈正相关(r=0.539,P=0.046)。BALF和血清中SP-D呈相同下降趋势,相关值为0.870(P=0.034)。
二氧化硅暴露确实导致了BALF和血清中SP含量的变化。血清中SP-C和SP-D含量可能作为矽肺的早期有效生物标志物。