益肾化瘀方对肾间质纤维化大鼠肾组织中PDGF-BB蛋白表达变化的影响
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摘要
目的:通过建立肾间质纤维化大鼠模型,动态观察模型大鼠血清尿素氮、肌酐,尿液中24h尿蛋白定量,肾组织中血小板衍生生长因子(PDGF-BB)蛋白表达变化及益肾化瘀方对以上观察指标的影响,探讨益肾化瘀方治疗肾间质纤维化的可能作用机制。
方法:将150只大鼠随机分为假手术组、模型组、洛汀新组、益肾化瘀方高剂量组、益肾化瘀方低剂量组,除假手术组外其余各组大鼠均采用单侧输尿管结扎的方法建立肾间质纤维化大鼠模型;分别于UUO术后3、7、14、21、28天,采用二乙酰-肟法观察模型大鼠血清尿素氮的变化,采用苦味酸法观察模型大鼠血清肌酐的变化,采用比色法观察模型大鼠尿液中24h尿蛋白定量的变化;采用组织病理学(HE、Masson染色)方法,观察模型大鼠肾组织形态结构的病理变化;采用Western Blot方法,观察模型大鼠肾组织中PDGF-BB蛋白表达变化,以β-actin为内参,测定PDGF-BB蛋白的相对表达量;综合观察益肾化瘀方对以上指标改变的影响。
结果:与假手术组相比,模型组大鼠血清尿素氮、肌酐均有不同程度增高, P<0.01;24h尿蛋白定量无明显变化;肾组织出现肾小管扩张、萎缩,蛋白管型,间质炎症细胞浸润,间质纤维化,并呈进行性加重;肾组织PDGF-BB蛋白表达3天后开始增加,模型组大鼠较假手术组显著增高,P<0.01,随时间延长,PDGF-BB蛋白表达逐渐增加。与模型组相比,各给药组大鼠肾功能得以改善,P<0.05或P<0.01;24h尿蛋白定量无明显变化;肾组织结构有所改善,肾小管扩张、萎缩,间质炎细胞浸润及纤维化程度均减轻;肾组织PDGF-BB蛋白的表达有所降低,P<0.01或P<0.05。
结论:该课题成功建立了肾间质纤维化大鼠模型,并从生化及肾脏病理改变得到证实;益肾化瘀方可以改善肾间质纤维化大鼠肾功能;可以改善肾组织病理改变;可以降低肾组织中PDGF-BB蛋白的表达。总之,益肾化瘀方可以用于治疗肾间质纤维化,但其机理仍需进一步深入研究。
Objectives: To set up rat models of Renal Interstitial Fibrosis. To investigate the protective influence of YiShenHuaYu(YSHY) on Serum Creatinine and Blood Uria Nitrogen and 24-hour Urine Protein, and the expression of Platelet Derived Growth Factor BB(PDGF-BB) in the Rat of Renal Interstitial Fibrosis. To disscuss some mechanisms of treating the Rat with Renal Interstitial Fibrosis.
Methods: The rats were randomly divided into sham-opration group, model group, Benazepril treatment group, YSHY high-dose and low-dose treatment group. Except sham-opration group, the other four groups were induced by unilateral ureteral obstruction (UUO) to set up RIF models. The rats were sacrificed at 3, 7, 14, 21 and 28 day. The change of Blood Uria Nitrogen was observed by using Two acetyl-oxime method, The change of Serum Creatinine was observed by using Picric acid method, The change of 24-hour Urine Protein was observed by using Colorimetry method, The alterations of renal constitution were detected by using the technique of Histopatholo- gy(the Haematoxylin and Eosin Staining、Masson Staining). The expressions of PDGF-BB in the kidneys were observed with theβ-actin as intrinsic control by using Western Blot. Meanwhile, the influences of YSHY on the above changes were studied.
Results: Compared to Sham-operation group, the level of serum creatinine and blood uria introgen was elevated gradually in rat models with P<0.01. Nonvisible changes can be seen on 24-hour urine protein. There were gradually serious ectatic and atrophy tubules, inflammatory cell infiltration and interstitial fibrosis. The expression of PDGF-BB was increased with the development of renal interstitial fibrosis from day 3 after UUO, and then gradually increased. Compared to models, all the changes mentioned above such as renal function, renal histopathologity were improved in the groups after given drugs. Mealwhile, Compared to models,all the indicators mentioned above were improved after given drugs with P<0.05 or P<0.01.
Conclusion: The rat model of RIF was established successfully which was confirmed through biochemistry and renal histopathological alteration. YSHY can improve the renal functions and renal constitution. RIF may be alleviated by decreasing expression of PDGF-BB. Although there is still much work to be done, we can draw a conclusion that YSHY can be used to treat Chronic Renal Failure.
方法:将150只大鼠随机分为假手术组、模型组、洛汀新组、益肾化瘀方高剂量组、益肾化瘀方低剂量组,除假手术组外其余各组大鼠均采用单侧输尿管结扎的方法建立肾间质纤维化大鼠模型;分别于UUO术后3、7、14、21、28天,采用二乙酰-肟法观察模型大鼠血清尿素氮的变化,采用苦味酸法观察模型大鼠血清肌酐的变化,采用比色法观察模型大鼠尿液中24h尿蛋白定量的变化;采用组织病理学(HE、Masson染色)方法,观察模型大鼠肾组织形态结构的病理变化;采用Western Blot方法,观察模型大鼠肾组织中PDGF-BB蛋白表达变化,以β-actin为内参,测定PDGF-BB蛋白的相对表达量;综合观察益肾化瘀方对以上指标改变的影响。
结果:与假手术组相比,模型组大鼠血清尿素氮、肌酐均有不同程度增高, P<0.01;24h尿蛋白定量无明显变化;肾组织出现肾小管扩张、萎缩,蛋白管型,间质炎症细胞浸润,间质纤维化,并呈进行性加重;肾组织PDGF-BB蛋白表达3天后开始增加,模型组大鼠较假手术组显著增高,P<0.01,随时间延长,PDGF-BB蛋白表达逐渐增加。与模型组相比,各给药组大鼠肾功能得以改善,P<0.05或P<0.01;24h尿蛋白定量无明显变化;肾组织结构有所改善,肾小管扩张、萎缩,间质炎细胞浸润及纤维化程度均减轻;肾组织PDGF-BB蛋白的表达有所降低,P<0.01或P<0.05。
结论:该课题成功建立了肾间质纤维化大鼠模型,并从生化及肾脏病理改变得到证实;益肾化瘀方可以改善肾间质纤维化大鼠肾功能;可以改善肾组织病理改变;可以降低肾组织中PDGF-BB蛋白的表达。总之,益肾化瘀方可以用于治疗肾间质纤维化,但其机理仍需进一步深入研究。
Objectives: To set up rat models of Renal Interstitial Fibrosis. To investigate the protective influence of YiShenHuaYu(YSHY) on Serum Creatinine and Blood Uria Nitrogen and 24-hour Urine Protein, and the expression of Platelet Derived Growth Factor BB(PDGF-BB) in the Rat of Renal Interstitial Fibrosis. To disscuss some mechanisms of treating the Rat with Renal Interstitial Fibrosis.
Methods: The rats were randomly divided into sham-opration group, model group, Benazepril treatment group, YSHY high-dose and low-dose treatment group. Except sham-opration group, the other four groups were induced by unilateral ureteral obstruction (UUO) to set up RIF models. The rats were sacrificed at 3, 7, 14, 21 and 28 day. The change of Blood Uria Nitrogen was observed by using Two acetyl-oxime method, The change of Serum Creatinine was observed by using Picric acid method, The change of 24-hour Urine Protein was observed by using Colorimetry method, The alterations of renal constitution were detected by using the technique of Histopatholo- gy(the Haematoxylin and Eosin Staining、Masson Staining). The expressions of PDGF-BB in the kidneys were observed with theβ-actin as intrinsic control by using Western Blot. Meanwhile, the influences of YSHY on the above changes were studied.
Results: Compared to Sham-operation group, the level of serum creatinine and blood uria introgen was elevated gradually in rat models with P<0.01. Nonvisible changes can be seen on 24-hour urine protein. There were gradually serious ectatic and atrophy tubules, inflammatory cell infiltration and interstitial fibrosis. The expression of PDGF-BB was increased with the development of renal interstitial fibrosis from day 3 after UUO, and then gradually increased. Compared to models, all the changes mentioned above such as renal function, renal histopathologity were improved in the groups after given drugs. Mealwhile, Compared to models,all the indicators mentioned above were improved after given drugs with P<0.05 or P<0.01.
Conclusion: The rat model of RIF was established successfully which was confirmed through biochemistry and renal histopathological alteration. YSHY can improve the renal functions and renal constitution. RIF may be alleviated by decreasing expression of PDGF-BB. Although there is still much work to be done, we can draw a conclusion that YSHY can be used to treat Chronic Renal Failure.
引文
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