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Hirudin Protects Against Kidney Damage in Streptozotocin-Induced Diabetic Nephropathy Rats by Inhibiting Inflammation via P38 MAPK/NF-κB Pathway.
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-08-07 , DOI: 10.2147/dddt.s257613 Jiarui Han 1, 2 , Xinxin Pang 1, 2 , Yage Zhang 1, 2 , Zining Peng 1, 2 , Xiujie Shi 1, 2 , Yufeng Xing 1, 2
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-08-07 , DOI: 10.2147/dddt.s257613 Jiarui Han 1, 2 , Xinxin Pang 1, 2 , Yage Zhang 1, 2 , Zining Peng 1, 2 , Xiujie Shi 1, 2 , Yufeng Xing 1, 2
Affiliation
Background: Inflammation-induced podocyte apoptosis plays an important role in kidney injury during diabetic nephropathy (DN). Hirudin (HIR), a natural compound extracted from leeches, can inhibit inflammation. However, whether HIR can protect the kidneys against inflammation during DN is unknown. In the present study, we aimed to study the effects of HIR on kidney damage in a DN rat model and explore its anti-inflammatory properties.
Methods: A streptozotocin-induced DN rat model was generated, and HIR was administered subcutaneously. Immortal podocytes and primary peritoneal macrophages were used for vitro studies. Hematoxylin and eosin staining was used to evaluate renal pathological changes; quantitative polymerase chain reaction and immunoblotting were used to detect gene expression; and TUNEL staining was used to detect apoptotic cells.
Results: Our results showed that HIR protected against renal injury, as indicated by kidney weight/body weight, serum creatinine, renal pathological changes, blood urea nitrogen, and detection of urine proteins. Notably, HIR treatment reduced macrophage infiltration, pro-inflammatory cytokine expression, and podocyte apoptosis in the kidney tissues of DN rats. In vitro, high glucose (HG) induced the activation of M1 macrophages, which was accompanied by increased podocyte apoptosis. HIR could decrease HG-induced podocyte apoptosis and suppress pro-inflammatory cytokine expression in podocytes in vitro. This was achieved via inhibition of p38 MAPK/NF-κB activation in renal tissues and podocytes.
Conclusion: HIR could inhibit inflammation via the p38 MAPK/NF-κB pathway, prevent podocyte apoptosis, and protect against kidney damage in a DN rat model.
中文翻译：
水蛭素通过 P38 MAPK/NF-κB 通路抑制炎症，保护链脲佐菌素诱导的糖尿病肾病大鼠免受肾脏损伤。
背景：炎症诱导的足细胞凋亡在糖尿病肾病（DN）的肾损伤中起重要作用。水蛭素（HIR）是一种从水蛭中提取的天然化合物，可以抑制炎症。然而，在 DN 期间，HIR 是否能保护肾脏免受炎症影响尚不清楚。在本研究中，我们旨在研究 HIR 对 DN 大鼠模型肾脏损伤的影响，并探索其抗炎特性。
方法：建立了链脲佐菌素诱导的 DN 大鼠模型，并皮下注射 HIR。永生足细胞和原代腹膜巨噬细胞用于体外研究。苏木精伊红染色评价肾脏病理变化；采用定量聚合酶链反应和免疫印迹法检测基因表达；TUNEL染色用于检测凋亡细胞。
结果：我们的结果表明，HIR 可防止肾损伤，如肾脏重量/体重、血清肌酐、肾脏病理变化、血尿素氮和尿蛋白检测所示。值得注意的是，HIR 治疗减少了 DN 大鼠肾脏组织中的巨噬细胞浸润、促炎细胞因子表达和足细胞凋亡。在体外，高糖 (HG) 诱导 M1 巨噬细胞的活化，伴随着足细胞凋亡的增加。在体外，HIR 可以减少 HG 诱导的足细胞凋亡并抑制足细胞中促炎细胞因子的表达。这是通过抑制肾组织和足细胞中的 p38 MAPK/NF-κB 活化来实现的。
结论：在 DN 大鼠模型中，HIR 可以通过 p38 MAPK/NF-κB 通路抑制炎症，防止足细胞凋亡，并防止肾损伤。
更新日期：2020-08-06
Methods: A streptozotocin-induced DN rat model was generated, and HIR was administered subcutaneously. Immortal podocytes and primary peritoneal macrophages were used for vitro studies. Hematoxylin and eosin staining was used to evaluate renal pathological changes; quantitative polymerase chain reaction and immunoblotting were used to detect gene expression; and TUNEL staining was used to detect apoptotic cells.
Results: Our results showed that HIR protected against renal injury, as indicated by kidney weight/body weight, serum creatinine, renal pathological changes, blood urea nitrogen, and detection of urine proteins. Notably, HIR treatment reduced macrophage infiltration, pro-inflammatory cytokine expression, and podocyte apoptosis in the kidney tissues of DN rats. In vitro, high glucose (HG) induced the activation of M1 macrophages, which was accompanied by increased podocyte apoptosis. HIR could decrease HG-induced podocyte apoptosis and suppress pro-inflammatory cytokine expression in podocytes in vitro. This was achieved via inhibition of p38 MAPK/NF-κB activation in renal tissues and podocytes.
Conclusion: HIR could inhibit inflammation via the p38 MAPK/NF-κB pathway, prevent podocyte apoptosis, and protect against kidney damage in a DN rat model.
中文翻译：
水蛭素通过 P38 MAPK/NF-κB 通路抑制炎症，保护链脲佐菌素诱导的糖尿病肾病大鼠免受肾脏损伤。
背景：炎症诱导的足细胞凋亡在糖尿病肾病（DN）的肾损伤中起重要作用。水蛭素（HIR）是一种从水蛭中提取的天然化合物，可以抑制炎症。然而，在 DN 期间，HIR 是否能保护肾脏免受炎症影响尚不清楚。在本研究中，我们旨在研究 HIR 对 DN 大鼠模型肾脏损伤的影响，并探索其抗炎特性。
方法：建立了链脲佐菌素诱导的 DN 大鼠模型，并皮下注射 HIR。永生足细胞和原代腹膜巨噬细胞用于体外研究。苏木精伊红染色评价肾脏病理变化；采用定量聚合酶链反应和免疫印迹法检测基因表达；TUNEL染色用于检测凋亡细胞。
结果：我们的结果表明，HIR 可防止肾损伤，如肾脏重量/体重、血清肌酐、肾脏病理变化、血尿素氮和尿蛋白检测所示。值得注意的是，HIR 治疗减少了 DN 大鼠肾脏组织中的巨噬细胞浸润、促炎细胞因子表达和足细胞凋亡。在体外，高糖 (HG) 诱导 M1 巨噬细胞的活化，伴随着足细胞凋亡的增加。在体外，HIR 可以减少 HG 诱导的足细胞凋亡并抑制足细胞中促炎细胞因子的表达。这是通过抑制肾组织和足细胞中的 p38 MAPK/NF-κB 活化来实现的。
结论：在 DN 大鼠模型中，HIR 可以通过 p38 MAPK/NF-κB 通路抑制炎症，防止足细胞凋亡，并防止肾损伤。
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