螺旋藻藻蓝蛋白抗百草枯诱导大鼠肺纤维化的研究
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摘要
海洋是药物的宝库，近年来，随着海洋生物学研究的不断深入，发现许多海洋藻类含有多种特有的天然的药用活性物质。藻蓝蛋白(Phycocyanin, PC)主要存在于蓝藻、红藻、隐藻和少数一些甲藻中，是藻胆蛋白的重要组分，在螺旋藻中的含量较高。研究表明，PC具有抗炎症、抗氧化、清除自由基、抗肿瘤等生理活性，为螺旋藻在保健和药用领域的开发提供重要的依据。
百草枯（Paraquat, PQ），是目前世界范围内应用最广泛的除草剂之一。随着在我国农业上的广泛应用，PQ中毒也日趋增多。PQ对人畜均有较强毒性，致死剂量小，发展快且无特效解毒药物，临床上病死率很高。肺为PQ中毒的主要靶器官，大剂量中毒常由于急性肺损伤所致的呼吸衰竭及心、肝、肾等多脏器功能衰竭而死亡；较小剂量的中毒往往引起迟发性的肺纤维化，病程相对较长，晚期多死于肺间质纤维化所致的呼吸衰竭。传统的糖皮质激素和细胞毒药物长期应用副作用大，疗效并不理想。因此寻找行之有效的治疗药物是目前医疗界迫切需要解决的问题。
PQ的中毒是多系统、多器官、多水平的，中毒机制尚未完全阐明，但多数学者认为，其中毒机制在于氧化损伤。PC能有效地清除氧基自由基，有较强抗氧化能力，对小鼠或大鼠炎症模型具有明显的抑制作用。这些活性作用对PQ中毒有潜在的治疗效果。目前，海洋药物尚未用于中毒治疗学研究，本课题研究的主要目的旨在研究PC对抗急性PQ中毒引起的急性肺损伤和肺纤维化作用，以期为临床救治和探索海洋药物治疗急性中毒提供科学依据。
本研究首先对钝顶螺旋藻中的PC进行了提取和纯化。采用磷酸盐缓冲液循环冻融联合超生波破碎法，50%硫酸铵沉淀获得PC，提取率达到13.2%。粗蛋白提取液再经过两次羟基磷灰石柱(HA)层析和sephacrylS-200HR凝胶层析对其进行纯化，纯度比（A620/A280）达到4.75。
然后我们对PC抗PQ诱导肺纤维化进行了研究：
（1）肺组织病理变化：①苏木精伊红染色法(hematoxylin-eosin staining, HE)：模型（PQ）组1-7d以急性肺泡炎为主要表现，3d时炎症表现最重，14-28d成纤维细胞增生，大量肺泡结构萎陷、破坏，胶原沉积，肺纤维化初步形成。PC组各观察点病理变化和模型组相似，但程度较轻。早期（3、7d）即肺泡炎期，肺泡渗出、细胞浸润少，中后期（14、28d）即肺纤维化进展和纤维化期，在胶原沉积，肺纤维化进展程度轻。②马松三色（Masson）染色：28d时模型组可见较多蓝色胶原沉积于支气管壁及肺泡间隔，蓝染面积百分比较对照组有显著性差异（P<0.01）。PC组蓝染胶原沉积较少，蓝染面积百分比较PQ组差异有显著性（P<0.05）。③电镜：PQ组：早期可见肺泡I型上皮细胞受损，纤毛脱失，基膜断裂，肺泡腔内有大量水肿渗出液，多见巨噬细胞，间质炎性细胞浸润；后期可见到肺泡间隔增厚，内含大量增生、肥大的肺泡n型上皮细胞，板层小体空泡化，多见异型核，肺泡隔内弹性纤维、胶原纤维和网状纤维多，胶原纤维增生明显。PC治疗后PQ中毒大鼠肺组织超微结构表现为肺泡炎及纤维增生减轻。
（2）血清和肺组织均浆丙二醛（MDA）含量变化：染毒后，染毒大鼠血清和肺组织均浆MDA含量均明显升高（P<0.01），PC治疗后，各观察点PC组MDA含量升高程度明显低于PQ组（P<0.01）。
（3）肺组织中羟脯氨酸（HYP）含量变化：染毒后，染毒大鼠肺组织均浆HYP含量均明显升高（P<0.01），PC治疗后，各观察点PC组HYP含量升高程度明显低于PQ组（P<0.01）。
（4）血清中谷胱甘肽过氧化物酶（GSH-Px）活力变化：染毒后，染毒大鼠血清中GSH-Px活力均明显降低（P<0.01），PC治疗后，各观察点PC组GSH-Px活力明显高于PQ组（P<0.01）。
（5）血清和肺组织均浆超氧化物歧化酶（SOD）活力变化：染毒后，染毒大鼠血清和肺组织中SOD活力均明显降低（P<0.01），PC治疗后，各观察点PC组SOD活力升高，与PQ组相比差异显著（P<0.01）。
（6）肺组织均浆细胞转化生长因子-β1（TGF-β1）的蛋白水平变化：染毒后，染毒大鼠肺组织中TGF-β1的蛋白水平均明显升高（P<0.01），PC治疗后，各观察点PC组TGF-β1的蛋白水平降低，与PQ组相比差异显著（P<0.01）。
（7）肺组织肿瘤坏死因子-α （TNF-α）、核因子-κB（NF-κB）的影响：染毒后，染毒大鼠肺组织中TNF-α的含量均明显升高(P<0.01)，3d时肺组织中TNF-α的含量最高，其后逐渐降低，28d时肺组织中TNF-α的含量最低。各观察时间点，PC组大鼠肺组织中TNF-α的含量均低于染毒组（P<0.01）。NF-κBp65的结果与TNF-α相似，7d时肺组织中NK-κBp65的含量最高，其后逐渐下降。各观察时间点，PC组大鼠肺组织中NK-κBp65的含量均低于染毒组（P<0.01）。结果表明：PC可以提高肺组织SOD和血浆GSH-Px、SOD活性，降低肺组织HYP、MDA和血浆MDA含量，降低肺纤维化大鼠肺组织TGF-β1的蛋白水平，抑制NF-κB亚基p65及TNF-α活性，减轻PQ中毒大鼠肺泡炎及后期纤维化程度，对PQ诱导的大鼠肺泡炎及肺纤维化具有显著的抑制作用，对PQ中毒有较好的治疗效果。该研究将为海洋药物治疗PQ中毒致肺纤维化提供新的思路。
Ocean is the treasure-house of potential pharmaceuticals. With the development ofmarine biological studies, many marine algae have been discovered to harbor many kindsof active substances with potential to be used as nutraceuticals and pharmaceuticals.Phycocyanin (PC), an important constituent of the phycobiliproteins，exits in cyanophytes,rhodophytes, some cryptophytes, and certain dinoflagellates. Recent studies on PC fromthe blue-green alga Spirulina platensis have demonstrated that PC has antioxidant,antimutagenic, antiviral, and anti-allergic effects. Paraquat (PQ), a highly toxic compoundfor humans and animals, is a world-widely used potent herbicide in agriculture. PQ ishighly toxic if swallowed as the concentrated product. Ingestion of large amounts isconsidered to be uniformly fatal, resulting in death from multi-organ failure andcardiogenic shock within several days. The exact mechanism of PQ toxicity is not knowncompletely, however, it has been demonstrated that the primary target organ for PQtoxicity is the lung. The most common cause of death from PQ poisoning is respiratoryfailure due to an oxidative insult to the pulmonary parenchyma with subsequentpulmonary fibrosis. PQ can release oxygen free radicals (superoxide and hydrogenperoxide) near the mucus membranes, promoting lipid peroxidation, resulting in mucosaldamages in different organs especially in the lung tissue. PQ has been widely used as anexperimental model to study lung injury, especially diffuse alveolar damage, due to its lowcost, rapid effect and simplicity of administration. Moreover, the mechanism ofpulmonary fibrosis induced by PQ in rats is similar to the fibrosis pathogenesis in humansexposed to this herbicide.
The common drugs used for PQ-poisoning treatment were glucocorticoid and cytotoxicdrugs. Glucocorticoid and cytotoxic drugs would expose some severe side effects whichcould result in the halt of treatment in the long-time usage, so it is now urgently requiredto solve problems directly for the effective treatment of drug.
PC has been reported to possess significant antioxidant and radical-scavengingproperties, offering protection against oxidative stress. It had been demonstrated that PCcould significantly inhibit doxorubicin induced oxidative stress and apoptosis in rat cardiomyocytes in vitro, and enhance the recovery of I/R-induced cardiac dysfunction andprotect the heart from apoptosis and injury through its antioxidant action. The presentstudies were designed to evaluate the effects of PC in rodent models on acute lung injuryand pulmonary fibrosis in rats induced by PQ, and to observe its potential therapeuticeffects in order to provide scientific basis for the treatment strategy of paraquat-inducedacute lung injury and pulmonary fibrosis.
Firstly, PC from Spirulina platensis were extracted and purified with improved methodsthrough repeatedly freezing and thawing alternatively in the presence of phosphate buffercombined with ultrasonic fragmentation. PC is efficiently extracted by precipitationusing50%(W/V) solid ammonium sulphated resulting in a recovery rate of13.2%. Then,the crude PC is chromatographed by hydroxylapatite (HA) column, futher purified bysephacry1S-200HR gel chromatoguaphy and HA column chromatography again. In theend, the purity of PC（A620/A280） was4.75.Furthermore, the curative effect of PC on pulmonary fibrosis in rats induced by paraquatwas investigated. The pathological changes of lung tissues:
①In HE staining, acute alveolitis was the chief performance of PQ group during the1d to7d, and the most inflammatory appeared at3d. The proliferation of fibroblasts could beobserved from14d to28d, alveolar structure collapsed and was destructed, collagendeposition and the initial formation of pulmonary fibrosis could also be observed. Thehistopathological changes in the PC group were milder than those in PQ-treated group ateach observed time. At the stage of pulmonary alveolitis (3d,7d), lung alveolus exudationand inflammatory cell infiltration were not common. At the stage of pulmonary fibrosis(14d,28d), collagen deposition and progression of pulmonary fibrosis were at a lesserextent.
②In Masson staining, a bulk of blue collagen deposition could be found on bronchial walland alveolar septum in PQ group. The percentage of positive area was much more than thecontrol group (P<0.01). The degree of blue collagen deposition was alleviated, and thepercentage of positive area of PC group.
③Electronic microscope observation：PQ group: In the early period, it could be foundimpaired epithelium alveolar epithelial cell I, falling cilia, broken basement membrance,and plenty of edema exudant in alveolar space. Macrophage and interstitial inflammatorycell infiltration could also be increasingly found. In the later period, the thickening ofalveolar septum which contained many of hyperplastic, hypertrophic alveolar epithelia type Ⅱ cells could be observed. It was also be observed the vacuolization of lamellatedbody and increasing allotype nucleus. The proliferation of elastic fibers, collagenous fibers,reticular fibers was increasingly found. The ultramicrostructure of lung tissues derivedfrom PC group were marked by alleviation of pulmonary alveolitis or fibrogenesiscompared to PQ group.
(2) The change of MDA in plasma and BALF of lung tissue: The contents of MDA inplasma and lung tissue were increased significantly (P<0.01) compared with the controlgroup after the treatment of PQ. While the content of MDA in plasma and lung tissue wasmarkedly decreased in PC group (P<0.01) compared with the PQ group.
(3) The change of HYP in BALF of lung tissue: The contents of MDA in lung tissuewere increased significantly (P<0.01) compared with the control group after the treatmentof PQ. While the content of MDA in lung tissue was markedly decreased in PC group(P<0.01) compared with the PQ group.
(4) The change of GSH-Px activity in plasma: The activity of GSH-Px in BALF wasdecreased significantly (P<0.01) compared with the control group after the treatment ofPQ. while the activity of GSH-Px was increased gradually in PC group, especially afterone week treatment (P<0.01).
(5)The change of SOD activity in plasma and BALF of lung tissue: The activity of SODin plasma and BALF was decreased significantly (P<0.01) compared with the controlgroup after the treatment of PQ. while the activity of SOD was increased markely in PCgroup compared with the PQ group (P<0.01).
(6) Effect of PC on the relative contents of NF-κB p65, TNF-α of lung injury rats Thepositive expressions of NF-κB, TNF-α of lung tissue were evidently in PQ group and PCgroup after given paraquat. Compared with the control group, the protein productions ofNF-κB p65and TNF–α in lung were promoted significantly in each observed time(P<0.01) in the PQ-treated group. Compared with PQ-treated group, the proteinproductions of NF-κB NF-κB p65and TNF-α in lung were inhibited (P<0.01) in the PCgroup.
In this experiment, it was found that PQ could significantly decrease the activity ofSOD and elevate the MDA content in plasma and BALF, which was in accordance withthe references. PC could inhibit the PQ-induced lipid peroxidation reaction, includingincrease of the SOD activity and decrease of the MDA content, and diminish the damageof cells and tissue in lungs as well as imrove the pathological damage induced by PQ. This result is in accord with the examination of pathological changes. PC could also alleviatethe TGF-β1expression in lung tissue. Compared with control group, the proteinproductions of NF-κB p65and TNF-α in lung were inhibited in the PQ-treated group.The histopathological changes in the PQ+PC-treated group were milder than those ofPQ-treated group. It suggested that PC possessed the effect of anti-pulmonary fibrosis.The results would provide the therapeutic evidence for developing the effective treatmentagents to pulmonary fibrosis from marine biological resources.
百草枯（Paraquat, PQ），是目前世界范围内应用最广泛的除草剂之一。随着在我国农业上的广泛应用，PQ中毒也日趋增多。PQ对人畜均有较强毒性，致死剂量小，发展快且无特效解毒药物，临床上病死率很高。肺为PQ中毒的主要靶器官，大剂量中毒常由于急性肺损伤所致的呼吸衰竭及心、肝、肾等多脏器功能衰竭而死亡；较小剂量的中毒往往引起迟发性的肺纤维化，病程相对较长，晚期多死于肺间质纤维化所致的呼吸衰竭。传统的糖皮质激素和细胞毒药物长期应用副作用大，疗效并不理想。因此寻找行之有效的治疗药物是目前医疗界迫切需要解决的问题。
PQ的中毒是多系统、多器官、多水平的，中毒机制尚未完全阐明，但多数学者认为，其中毒机制在于氧化损伤。PC能有效地清除氧基自由基，有较强抗氧化能力，对小鼠或大鼠炎症模型具有明显的抑制作用。这些活性作用对PQ中毒有潜在的治疗效果。目前，海洋药物尚未用于中毒治疗学研究，本课题研究的主要目的旨在研究PC对抗急性PQ中毒引起的急性肺损伤和肺纤维化作用，以期为临床救治和探索海洋药物治疗急性中毒提供科学依据。
本研究首先对钝顶螺旋藻中的PC进行了提取和纯化。采用磷酸盐缓冲液循环冻融联合超生波破碎法，50%硫酸铵沉淀获得PC，提取率达到13.2%。粗蛋白提取液再经过两次羟基磷灰石柱(HA)层析和sephacrylS-200HR凝胶层析对其进行纯化，纯度比（A620/A280）达到4.75。
然后我们对PC抗PQ诱导肺纤维化进行了研究：
（1）肺组织病理变化：①苏木精伊红染色法(hematoxylin-eosin staining, HE)：模型（PQ）组1-7d以急性肺泡炎为主要表现，3d时炎症表现最重，14-28d成纤维细胞增生，大量肺泡结构萎陷、破坏，胶原沉积，肺纤维化初步形成。PC组各观察点病理变化和模型组相似，但程度较轻。早期（3、7d）即肺泡炎期，肺泡渗出、细胞浸润少，中后期（14、28d）即肺纤维化进展和纤维化期，在胶原沉积，肺纤维化进展程度轻。②马松三色（Masson）染色：28d时模型组可见较多蓝色胶原沉积于支气管壁及肺泡间隔，蓝染面积百分比较对照组有显著性差异（P<0.01）。PC组蓝染胶原沉积较少，蓝染面积百分比较PQ组差异有显著性（P<0.05）。③电镜：PQ组：早期可见肺泡I型上皮细胞受损，纤毛脱失，基膜断裂，肺泡腔内有大量水肿渗出液，多见巨噬细胞，间质炎性细胞浸润；后期可见到肺泡间隔增厚，内含大量增生、肥大的肺泡n型上皮细胞，板层小体空泡化，多见异型核，肺泡隔内弹性纤维、胶原纤维和网状纤维多，胶原纤维增生明显。PC治疗后PQ中毒大鼠肺组织超微结构表现为肺泡炎及纤维增生减轻。
（2）血清和肺组织均浆丙二醛（MDA）含量变化：染毒后，染毒大鼠血清和肺组织均浆MDA含量均明显升高（P<0.01），PC治疗后，各观察点PC组MDA含量升高程度明显低于PQ组（P<0.01）。
（3）肺组织中羟脯氨酸（HYP）含量变化：染毒后，染毒大鼠肺组织均浆HYP含量均明显升高（P<0.01），PC治疗后，各观察点PC组HYP含量升高程度明显低于PQ组（P<0.01）。
（4）血清中谷胱甘肽过氧化物酶（GSH-Px）活力变化：染毒后，染毒大鼠血清中GSH-Px活力均明显降低（P<0.01），PC治疗后，各观察点PC组GSH-Px活力明显高于PQ组（P<0.01）。
（5）血清和肺组织均浆超氧化物歧化酶（SOD）活力变化：染毒后，染毒大鼠血清和肺组织中SOD活力均明显降低（P<0.01），PC治疗后，各观察点PC组SOD活力升高，与PQ组相比差异显著（P<0.01）。
（6）肺组织均浆细胞转化生长因子-β1（TGF-β1）的蛋白水平变化：染毒后，染毒大鼠肺组织中TGF-β1的蛋白水平均明显升高（P<0.01），PC治疗后，各观察点PC组TGF-β1的蛋白水平降低，与PQ组相比差异显著（P<0.01）。
（7）肺组织肿瘤坏死因子-α （TNF-α）、核因子-κB（NF-κB）的影响：染毒后，染毒大鼠肺组织中TNF-α的含量均明显升高(P<0.01)，3d时肺组织中TNF-α的含量最高，其后逐渐降低，28d时肺组织中TNF-α的含量最低。各观察时间点，PC组大鼠肺组织中TNF-α的含量均低于染毒组（P<0.01）。NF-κBp65的结果与TNF-α相似，7d时肺组织中NK-κBp65的含量最高，其后逐渐下降。各观察时间点，PC组大鼠肺组织中NK-κBp65的含量均低于染毒组（P<0.01）。结果表明：PC可以提高肺组织SOD和血浆GSH-Px、SOD活性，降低肺组织HYP、MDA和血浆MDA含量，降低肺纤维化大鼠肺组织TGF-β1的蛋白水平，抑制NF-κB亚基p65及TNF-α活性，减轻PQ中毒大鼠肺泡炎及后期纤维化程度，对PQ诱导的大鼠肺泡炎及肺纤维化具有显著的抑制作用，对PQ中毒有较好的治疗效果。该研究将为海洋药物治疗PQ中毒致肺纤维化提供新的思路。
Ocean is the treasure-house of potential pharmaceuticals. With the development ofmarine biological studies, many marine algae have been discovered to harbor many kindsof active substances with potential to be used as nutraceuticals and pharmaceuticals.Phycocyanin (PC), an important constituent of the phycobiliproteins，exits in cyanophytes,rhodophytes, some cryptophytes, and certain dinoflagellates. Recent studies on PC fromthe blue-green alga Spirulina platensis have demonstrated that PC has antioxidant,antimutagenic, antiviral, and anti-allergic effects. Paraquat (PQ), a highly toxic compoundfor humans and animals, is a world-widely used potent herbicide in agriculture. PQ ishighly toxic if swallowed as the concentrated product. Ingestion of large amounts isconsidered to be uniformly fatal, resulting in death from multi-organ failure andcardiogenic shock within several days. The exact mechanism of PQ toxicity is not knowncompletely, however, it has been demonstrated that the primary target organ for PQtoxicity is the lung. The most common cause of death from PQ poisoning is respiratoryfailure due to an oxidative insult to the pulmonary parenchyma with subsequentpulmonary fibrosis. PQ can release oxygen free radicals (superoxide and hydrogenperoxide) near the mucus membranes, promoting lipid peroxidation, resulting in mucosaldamages in different organs especially in the lung tissue. PQ has been widely used as anexperimental model to study lung injury, especially diffuse alveolar damage, due to its lowcost, rapid effect and simplicity of administration. Moreover, the mechanism ofpulmonary fibrosis induced by PQ in rats is similar to the fibrosis pathogenesis in humansexposed to this herbicide.
The common drugs used for PQ-poisoning treatment were glucocorticoid and cytotoxicdrugs. Glucocorticoid and cytotoxic drugs would expose some severe side effects whichcould result in the halt of treatment in the long-time usage, so it is now urgently requiredto solve problems directly for the effective treatment of drug.
PC has been reported to possess significant antioxidant and radical-scavengingproperties, offering protection against oxidative stress. It had been demonstrated that PCcould significantly inhibit doxorubicin induced oxidative stress and apoptosis in rat cardiomyocytes in vitro, and enhance the recovery of I/R-induced cardiac dysfunction andprotect the heart from apoptosis and injury through its antioxidant action. The presentstudies were designed to evaluate the effects of PC in rodent models on acute lung injuryand pulmonary fibrosis in rats induced by PQ, and to observe its potential therapeuticeffects in order to provide scientific basis for the treatment strategy of paraquat-inducedacute lung injury and pulmonary fibrosis.
Firstly, PC from Spirulina platensis were extracted and purified with improved methodsthrough repeatedly freezing and thawing alternatively in the presence of phosphate buffercombined with ultrasonic fragmentation. PC is efficiently extracted by precipitationusing50%(W/V) solid ammonium sulphated resulting in a recovery rate of13.2%. Then,the crude PC is chromatographed by hydroxylapatite (HA) column, futher purified bysephacry1S-200HR gel chromatoguaphy and HA column chromatography again. In theend, the purity of PC（A620/A280） was4.75.Furthermore, the curative effect of PC on pulmonary fibrosis in rats induced by paraquatwas investigated. The pathological changes of lung tissues:
①In HE staining, acute alveolitis was the chief performance of PQ group during the1d to7d, and the most inflammatory appeared at3d. The proliferation of fibroblasts could beobserved from14d to28d, alveolar structure collapsed and was destructed, collagendeposition and the initial formation of pulmonary fibrosis could also be observed. Thehistopathological changes in the PC group were milder than those in PQ-treated group ateach observed time. At the stage of pulmonary alveolitis (3d,7d), lung alveolus exudationand inflammatory cell infiltration were not common. At the stage of pulmonary fibrosis(14d,28d), collagen deposition and progression of pulmonary fibrosis were at a lesserextent.
②In Masson staining, a bulk of blue collagen deposition could be found on bronchial walland alveolar septum in PQ group. The percentage of positive area was much more than thecontrol group (P<0.01). The degree of blue collagen deposition was alleviated, and thepercentage of positive area of PC group.
③Electronic microscope observation：PQ group: In the early period, it could be foundimpaired epithelium alveolar epithelial cell I, falling cilia, broken basement membrance,and plenty of edema exudant in alveolar space. Macrophage and interstitial inflammatorycell infiltration could also be increasingly found. In the later period, the thickening ofalveolar septum which contained many of hyperplastic, hypertrophic alveolar epithelia type Ⅱ cells could be observed. It was also be observed the vacuolization of lamellatedbody and increasing allotype nucleus. The proliferation of elastic fibers, collagenous fibers,reticular fibers was increasingly found. The ultramicrostructure of lung tissues derivedfrom PC group were marked by alleviation of pulmonary alveolitis or fibrogenesiscompared to PQ group.
(2) The change of MDA in plasma and BALF of lung tissue: The contents of MDA inplasma and lung tissue were increased significantly (P<0.01) compared with the controlgroup after the treatment of PQ. While the content of MDA in plasma and lung tissue wasmarkedly decreased in PC group (P<0.01) compared with the PQ group.
(3) The change of HYP in BALF of lung tissue: The contents of MDA in lung tissuewere increased significantly (P<0.01) compared with the control group after the treatmentof PQ. While the content of MDA in lung tissue was markedly decreased in PC group(P<0.01) compared with the PQ group.
(4) The change of GSH-Px activity in plasma: The activity of GSH-Px in BALF wasdecreased significantly (P<0.01) compared with the control group after the treatment ofPQ. while the activity of GSH-Px was increased gradually in PC group, especially afterone week treatment (P<0.01).
(5)The change of SOD activity in plasma and BALF of lung tissue: The activity of SODin plasma and BALF was decreased significantly (P<0.01) compared with the controlgroup after the treatment of PQ. while the activity of SOD was increased markely in PCgroup compared with the PQ group (P<0.01).
(6) Effect of PC on the relative contents of NF-κB p65, TNF-α of lung injury rats Thepositive expressions of NF-κB, TNF-α of lung tissue were evidently in PQ group and PCgroup after given paraquat. Compared with the control group, the protein productions ofNF-κB p65and TNF–α in lung were promoted significantly in each observed time(P<0.01) in the PQ-treated group. Compared with PQ-treated group, the proteinproductions of NF-κB NF-κB p65and TNF-α in lung were inhibited (P<0.01) in the PCgroup.
In this experiment, it was found that PQ could significantly decrease the activity ofSOD and elevate the MDA content in plasma and BALF, which was in accordance withthe references. PC could inhibit the PQ-induced lipid peroxidation reaction, includingincrease of the SOD activity and decrease of the MDA content, and diminish the damageof cells and tissue in lungs as well as imrove the pathological damage induced by PQ. This result is in accord with the examination of pathological changes. PC could also alleviatethe TGF-β1expression in lung tissue. Compared with control group, the proteinproductions of NF-κB p65and TNF-α in lung were inhibited in the PQ-treated group.The histopathological changes in the PQ+PC-treated group were milder than those ofPQ-treated group. It suggested that PC possessed the effect of anti-pulmonary fibrosis.The results would provide the therapeutic evidence for developing the effective treatmentagents to pulmonary fibrosis from marine biological resources.
引文
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