禾肾丸通过调控ANGPTL3治疗阿霉素肾病大鼠蛋白尿及血脂代谢紊乱的实验研究

    Experimental study of Heshen pill on the treatment of proteinuria and dyslipidemia in rats with adriamycin nephropathy through the regulation of ANGPTL3

    • 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1 d及造模后第2、4、6、8周末24 h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24 h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1 d 24 h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24 h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24 h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24 h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).The 24 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.

       

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