摘要
目的观察舒洛地特对膜性肾病(MN)大鼠肾组织中podocin、nephrin表达的影响,探讨舒洛地特对MN的保护作用。方法将40只SD大鼠随机分为正常对照组(A组)、模型组(B组)、低剂量舒洛地特组(C组)、高剂量舒洛地特组(D组),每组各10只。除A组外,其他3组大鼠进行MN模型制备。造模成功后,C组和D组每只大鼠分别按照舒洛地特10 mg/kg、20 mg/kg剂量溶于生理盐水配成溶液灌胃,A、B组每只大鼠给予相同剂量生理盐水灌胃,均连续4周。各组大鼠分别于造模前、后及药物干预4周后检测24 h尿蛋白定量,在光镜和电镜下分别观察不同染色的大鼠肾组织病理形态。采用免疫组化检测大鼠肾组织podocin、nephrin平均积分光密度(IOD)。结果造模后,与A组比较,B、C、D组大鼠24 h尿蛋白定量均显著升高(P<0.05)。治疗后,C、D组大鼠24 h尿蛋白定量较同组造模后及B组同期均降低,D组24 h尿蛋白定量较C组同期显著降低(P<0.05)。光镜下,A组大鼠肾小球无固有细胞增多,无基底膜增厚;B组大鼠肾小球固有细胞增多,基底膜明显增厚;C、D组大鼠肾小球固有细胞轻度增多,基底膜增厚较B组减轻。电镜下,A组大鼠肾小球足细胞结构清晰,足突排列整齐;B组大鼠肾小球基底膜弥漫增厚,足突广泛融合或消失;C组大鼠肾小球基底膜不规则增厚,足突部分融合;D组大鼠肾小球基底膜轻度增厚,足突部分融合。与A组比较,B、C、D组大鼠podocin、nephrin IOD均降低;与B组比较,C、D组大鼠podocin、nephrin IOD均升高;与C组相比较,D组大鼠podocin、nephrin IOD均升高(P<0.05)。结论舒洛地特可降低MN大鼠24 h尿蛋白定量,上调MN大鼠肾组织中podocin、nephrin的表达,且上述作用具有剂量依赖性。
Objective To observe the effect of sulodexide on expression of podocin and nephrin in renal tissues of membranous nephropathy(MN)rats,and to explore the protective mechanism of sulodexide on MN.Methods Forty SD rats were randomly divided into normal control group(group A),model group(group B),low-dose sulodexide group(group C)and high-dose sulodexide group(group D),with 10 rats in each group.Except group A,the other three groups were prepared with MN model.After successful modeling,each rat in group C and group D was intragastric with sulodexide at the dose of 10 mg/kg and 20 mg/kg of normal saline,respectively.Each rat in group A and B was intragastric with the same dose of normal saline,for consecutive 4 weeks.The 24 h urinary protein was detected before and after modeling and 4 weeks after drug intervention.The pathological morphology of kidney tissues of rats with different staining were observed under light microscope and electron microscope.Immunohistochemistry was used to detect the mean integral optical density(IOD)of podocin and nephrin in rat kidney tissue.Results After modeling,compared with group A,the 24 h urinary protein in group B,C and D were significantly increased(P<0.05).After treatment,the 24 h urinary protein in group C and D were lower than those in group B and group C after modeling,the 24 h urinary protein in group D was significantly lower than that in group C(P<0.05).Under light microscope,there were no increase of proper cells in the glomerulus of group A and no thickening of basement membrane.In group B,glomerular proper cells were increased and basement membrane was significantly thickened.Glomerular proper cells increased slightly in group C and D,and basement membrane thickened less than that in group B.Under electron microscope,the podocyte structure of group A was clear and the foot processes were arranged neatly.In group B,the glomerular basement membrane was diffusely thickened and the foot processes were extensively fused or disappeared.In group C,the glomerular basement membrane was irregularly thickened and the foot process was partially fused.In group D,basement membrane was slightly thickened and part of foot process was fused.Compared with group A,podocin and nephrin IOD were decreased in group B,C and D;Compared with group B,podocin and nephrin IOD were increased in group C and D;Compared with group C,podocin and Nephrin IOD were significantly increased in group D(P<0.05).Conclusion sulodexide can reduce the 24 h urinary protein in MN rats,and can up-regulate the expression of podocin and nephrin in MN rats kidney tissue,and above effect is dose-dependent.
作者
吝娜
曹磊
王保兴
Lin Na;Cao Lei;Wang Baoxing(Second Department of Neurology,Shijiazhuang Huayao hospital,North China Medical Health Group,Shijiazhuang 050051,China;不详)
出处
《临床内科杂志》
CAS
2022年第7期481-485,共5页
Journal of Clinical Internal Medicine
基金
河北省医学科学研究课题(20221564)
