摘要
目的:探讨禾肾丸通过调控血管生成素样蛋白3(ANGPTL3)治疗阿霉素肾病大鼠蛋白尿及血脂代谢紊乱的作用机制.方法:50 只雄性SD大鼠随机分为5 组,每组10 只,空白组:不作特殊处理,仅予以每日清晨蒸馏水灌胃;模型组:造模成功后每日清晨蒸馏水灌胃;禾肾丸组:造模成功后每日清晨以禾肾丸灌胃;对照组:造模成功后每日清晨以泼尼松灌胃;联合用药组:造模成功后每日清晨以泼尼松、禾肾丸灌胃,各组均灌胃8 周.密切观察各组大鼠造模及研究期间各种行为学改变,检测和比较各组大鼠造模前1d及造模后第2、4、6、8 周末24h尿蛋白水平,同时检测和比较各组大鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)等血脂指标及血清ANGPTL3 表达水平.分析各组大鼠血清ANGPTL3 表达水平与血脂指标及造模后第8 周末24h尿蛋白水平的相关性.结果:禾肾丸组、对照组及联合用药组大鼠造模后第8 周各种行为学改变均优于模型组;各组大鼠造模前1d24h尿蛋白水平比较差异无统计学意义(P>0.05),造模后第2、4 周模型组、禾肾丸组、对照组及联合用药组大鼠24h尿蛋白水平均明显高于空白组(P<0.05),而组间比较差异无统计学意义(P>0.05),造模后第 6、8 周禾肾丸组、对照组大鼠 24h尿蛋白水平明显高于联合用药组和低于模型组(P<0.05),而禾肾丸组与对照组比较差异无统计学意义(P>0.05);模型组、禾肾丸组、对照组及联合用药组大鼠TC、TG、LDL-C等血脂指标及血清ANGPTL3 表达水平均明显高于空白组(P<0.05),而HDL均明显低于空白组(P<0.05),且禾肾丸组、对照组大鼠TC、TG、LDL-C及ANGPTL3 均低于模型组和高于联合用药组(P<0.05),HDL-C均高于模型组和低于联合用药组(P<0.05),而禾肾丸组与对照组比较差异无统计学意义(P>0.05);各组大鼠血清ANGPTL3 表达水平与TC、TG、LDL-C及24h尿蛋白均呈正相关关系(P<0.05～P<0.01),而与HDL-C呈负相关关系(P<0.05～P<0.01).结论:禾肾丸可能通过调控ANGPTL3 而起到治疗阿霉素肾病大鼠蛋白尿及血脂代谢紊乱的作用.
Abstract
Objective:To investigate the mechanism of Heshen pill in the treatment of proteinuria and dyslipidemia in adriamycin nephropathy rats through the regulation of angiopogenin-like protein 3(ANGPTL3).Methods:Fifty male SD rats were randomly divided into 5 groups with 10 rats in each group.The blank group was given distilled water by gavage every morning without special treatment;the model group was given distilled water by gavage every morning after successful modeling;the Heshen pill group was given Heshen pill by gavage every morning after successful modeling;the control group was given prednisone by gavage every morning after successful modeling;the combined treatment group was given prednisone and Heshen pill by gavage every morning after successful modeling.Each group was gavaged for 8 weeks.The behavioral changes of rats in each group were closely observed during the period of modeling and the research.The levels of 24 h urinary protein at 1 day before modeling and at the end of 2,4,6,and 8 weeks after modeling were detected and compared.At the same time,the various serum lipid indexes such as TC,TG,LDL-C,HDL-C,and serum expression level of ANGPTL3 were detected and compared.The correlation between serum ANGPTL3 expression level and blood lipid indexes,24 h urinary protein level at the end of the eighth week after modeling was analyzed.Results:All behavioral changes of rats in Heshen pill group,control group,and combined treatment group were better than that in model group at 8 weeks after modeling.There was no significant difference in the 24 h urinary protein level before 1 d of modeling among all groups(P>0.05).The24 h urinary protein levels in the model group,Heshen pill group,control group,and combined treatment group were all significantly higher than that in blank group at 2 and 4 weeks after modeling(P<0.05),while there was no significant difference among each group(P>0.05).The 24 h urinary protein levels in Heshen pill group and control group were significantly higher than that in combined treatment group and lower than that in model group at 6 and 8 weeks after modeling(P<0.05),but there was no significant difference between Heshen pill group and control group(P>0.05).The serum lipid indexes,including TC,TG,LDL-C,and the expression level of serum ANGPTL3 in model group,Heshen pill group,control group and combined treatment group were significantly higher than those in blank group(P<0.05),while the HDL-C in each group was significantly lower than that in blank group(P<0.05).TC,TG,LDL-C and ANGPTL3 in Heshen pill group and control group were lower than those in model group and combined treatment group(P<0.05).HDL-C was higher than those in model group and combined treatment group(P<0.05),while there was no statistical significance between Heshen pill group and control group(P>0.05).The expression level of serum ANGPTL3 in each group was positively correlated with TC,TG,LDL-C and 24 h urine protein(P<0.05 to P<0.01),while negatively correlated with HDL-C(P<0.05 to P<0.01).Conclusions:Heshen pill may play a role in treatment of albuminuria and dyslipidemia in rats with adriamycin nephropathy through the regulation of ANGPTL3.
基金项目
湖南省卫生健康委科研课题(202103050979)
湖南中医药大学校级科研基金项目(2019XJJJ055)
NETL
NSTL
维普
万方数据