Conclusions
Hypertensive renal damage mice display elevated expression of LRG-1 in serum and kidney, and irbesartan can reduce the expression of LRG-1 while alleviating renal damage. The level of serum LRG-1 is positively correlated with the degree of hypertensive renal damage, suggesting that it may participate in the occurrence and development of hypertensive renal damage. 目的: 长期的血压升高可能导致肾损伤，而高血压肾损害的发病机制尚不清楚。本研究通过检测高血压肾损害小鼠血清及肾组织中富含亮氨酸α-2糖蛋白-1(leucine-rich alpha-2-glycoprotein-1，LRG-1)的表达，分析其与相关指标的关系，探讨其在高血压肾损害中的作用及意义。方法: 以C57BL/6小鼠为研究对象，将其随机分为对照组、血管紧张素II(angiotensin II，Ang II)组和Ang II+厄贝沙坦组(n=5)。对照组用生理盐水灌胃；Ang II组用Ang II以1.5 mg/(kg·d)的速度持续皮下泵入28 d构建高血压肾损害小鼠模型，再用等量生理盐水灌胃；Ang II+厄贝沙坦组用相同方法构建高血压肾损害小鼠模型，再用厄贝沙坦灌胃。运用免疫组织化学法及蛋白质印迹法检测肾组织中LRG-1及纤维化相关指标(I型胶原和纤维连接蛋白)的表达，酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测各组小鼠血清LRG-1及相关炎症因子水平，检测小鼠的尿蛋白-肌酐比值及肾功能，并进行相关性分析。结果: 与对照组相比，Ang II组小鼠血清LRG-1水平升高，肾组织LRG-1蛋白、I型胶原及纤维连接蛋白表达增加(均P<0.01)。经过厄贝沙坦治疗后，高血压小鼠肾损害减轻，血清及肾组织LRG-1水平降低，肾组织I型胶原及纤维连接蛋白表达下调(均P<0.01)。直线相关分析显示：高血压肾损害小鼠血清LRG-1水平与尿蛋白-肌酐比值、血尿素氮及血肌酐水平呈正相关；血清LRG-1水平与血清炎症因子TNF-α、IL-1β及IL-6呈正相关。结论: 高血压肾损害小鼠血清及肾组织LRG-1表达增加，厄贝沙坦在减轻肾损害的同时可以降低LRG-1的表达；血清LRG-1水平与高血压肾损害程度及炎症反应呈正相关，提示其可能参与高血压肾损害的发生、发展。.
Methods
C57BL/6 mice were used in this study and randomly divided into a control group, an angiotensin II (Ang II) group, and an Ang II+irbesartan group. The control group was gavaged with physiological saline. The Ang II group was pumped subcutaneously at a rate of 1.5 mg/(kg·d) for 28 days to establish the hypertensive renal damage model in mice, and then gavaged with equivalent physiological saline. The Ang II+irbesartan group used the same method to establish the hypertensive renal damage model, and then was gavaged with irbesartan. Immunohistochemistry and Western blotting were used to detect the expression of LRG-1 and fibrosis-related indicators (collagen I and fibronectin) in renal tissues. ELISA was used to evaluate the level of serum LRG-1 and inflammatory cytokines in mice. The urinary protein-creatinine ratio and renal function were determined, and correlation analysis was conducted.
Results
Compared with the control group, the levels of serum LRG-1, the expression of LRG-1 protein, collagen I, and fibronectin in kidney in the Ang II group were increased (all P<0.01). After treating with irbesartan, renal damage of hypertensive mice was alleviated, while the levels of LRG-1 in serum and kidney were decreased, and the expression of collagen I and fibronectin was down-regulated (all P<0.01). Correlation analysis showed that the level of serum LRG-1 was positively correlated with urinary protein-creatinine ratio, blood urea nitrogen, and blood creatinine level in hypertensive kidney damage mice. Serum level of LRG-1 was also positively correlated with serum inflammatory factors including TNF-α, IL-1β, and IL-6. Conclusions: Hypertensive renal damage mice display elevated expression of LRG-1 in serum and kidney, and irbesartan can reduce the expression of LRG-1 while alleviating renal damage. The level of serum LRG-1 is positively correlated with the degree of hypertensive renal damage, suggesting that it may participate in the occurrence and development of hypertensive renal damage. 目的: 长期的血压升高可能导致肾损伤，而高血压肾损害的发病机制尚不清楚。本研究通过检测高血压肾损害小鼠血清及肾组织中富含亮氨酸α-2糖蛋白-1(leucine-rich alpha-2-glycoprotein-1，LRG-1)的表达，分析其与相关指标的关系，探讨其在高血压肾损害中的作用及意义。方法: 以C57BL/6小鼠为研究对象，将其随机分为对照组、血管紧张素II(angiotensin II，Ang II)组和Ang II+厄贝沙坦组(n=5)。对照组用生理盐水灌胃；Ang II组用Ang II以1.5 mg/(kg·d)的速度持续皮下泵入28 d构建高血压肾损害小鼠模型，再用等量生理盐水灌胃；Ang II+厄贝沙坦组用相同方法构建高血压肾损害小鼠模型，再用厄贝沙坦灌胃。运用免疫组织化学法及蛋白质印迹法检测肾组织中LRG-1及纤维化相关指标(I型胶原和纤维连接蛋白)的表达，酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测各组小鼠血清LRG-1及相关炎症因子水平，检测小鼠的尿蛋白-肌酐比值及肾功能，并进行相关性分析。结果: 与对照组相比，Ang II组小鼠血清LRG-1水平升高，肾组织LRG-1蛋白、I型胶原及纤维连接蛋白表达增加(均P<0.01)。经过厄贝沙坦治疗后，高血压小鼠肾损害减轻，血清及肾组织LRG-1水平降低，肾组织I型胶原及纤维连接蛋白表达下调(均P<0.01)。直线相关分析显示：高血压肾损害小鼠血清LRG-1水平与尿蛋白-肌酐比值、血尿素氮及血肌酐水平呈正相关；血清LRG-1水平与血清炎症因子TNF-α、IL-1β及IL-6呈正相关。结论: 高血压肾损害小鼠血清及肾组织LRG-1表达增加，厄贝沙坦在减轻肾损害的同时可以降低LRG-1的表达；血清LRG-1水平与高血压肾损害程度及炎症反应呈正相关，提示其可能参与高血压肾损害的发生、发展。.