Progress in the study of the role of mitochondrial homeostasis in the pathogenesis of chronic kidney disease

doi:10.3877/cma.j.issn.2095-3216.2025.05.006

Abstract

Abstract:

Mitochondrial homeostasis is crucial for maintaining normal kidney function. This article reviewed the research progress on the role of mitochondrial biogenesis, bioenergetics, kinetics, autophagy, and other mitochondrial homeostasis regulatory factors in the pathogenesis of chronic kidney disease, and elaborated on the current status and prospects of drug development for treating chronic kidney disease by restoring mitochondrial homeostasis.

Key words: Chronic kidney disease, Mitochondrial homeostasis, Targeted treatment

Xinrui Li, Mingzhu Jiang, Ping Shi, Hongbin Mou. Progress in the study of the role of mitochondrial homeostasis in the pathogenesis of chronic kidney disease[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2025, 14(05): 276-287.

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References 74

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药物名称	成分/机制	慢性肾脏病模型	肾脏疗效	反映线粒体生物合成的指标	参考文献
APX115	Nox抑制剂	STZ诱导DKD小鼠	1.减少蛋白尿 2.改善肾小球肥大、肾小管和足细胞损伤以及肾纤维化 3.减少肾脏脂质沉积、炎症、氧化应激	1. PGC-1α 2. NRF1、TFAM	[9]
葡萄籽原花青素提取物	多酚	STZ诱导DKD大鼠	1.改善系膜扩张、改善足突融合和基底膜增厚 2.减轻凋亡	SIRT1、PGC-1α、NRF1、TFAM	[10]
荔枝多酚	多酚	db/db小鼠(DKD)	改善系膜扩张、肾小球肥大	1. SIRT1、PGC-1α、NRF1、TFAM 2.呼吸链复合物亚基表达量	[11]
红景天苷	2-(4-羟基苯基)乙基β-D-吡喃葡萄糖苷	STZ诱导DKD小鼠	1.减少白蛋白尿；降低血清肌酐、血尿素氮 2.改善肾小球肥大、足突融合以及肾纤维化；减少纤维化蛋白表达(Col-Ⅰ、FN、α-SMA)	1. SIRT1、PGC-1α 2.呼吸链复合物亚基表达量 3. mtDNA含量	[12]
脂联素	血浆激素蛋白	STZ诱导DKD大鼠＋高糖刺激NRK-52E细胞	1.减少蛋白尿；降低血清肌酐、血尿素氮 2.改善系膜扩张、基底膜增厚	1. PGC-1α、TFAM 2.呼吸链复合物亚基表达量 3. mtDNA含量	[13]
萝卜硫素	异硫氰酸酯	UUO大鼠	减缓小管损伤、坏死；减少纤维化蛋白表达(α-SMA)	1.呼吸链复合物亚基表达量 2.线粒体数量的标志物VDAC和ANT密度分析	[14]
蒿甲醚		阿霉素肾病小鼠	1.降低尿蛋白/肌酐比 2.改善肾小管损伤、肾小管表型转变	NRF1、TFAM	[15]
绿茶多酚	有效活性成分包括表没食子儿茶素没食子酸酯(占比47.2%)等	环孢素肾病大鼠	1.降低血清肌酐 2.改善肾小管损伤、肾纤维化	1. PGC-1 α、TFAM 2.呼吸链复合物亚基表达量 3. mtDNA含量	[16]
水飞蓟素	至少6种主要的同分异构体黄酮类化合物和少量黄酮类化合物	高脂喂养小鼠＋HK细胞(棕榈酸刺激)	1.改善肾小球系膜扩张、胶原沉积 2.减少肾脏脂质沉积和活性氧自由基生成	1. PGC-1α、NRF2、TFAM 2.线粒体DNA含量	[17]
一系列异黄酮	大豆黄酮和刺芒柄花素诱导肾小管上皮细胞中SIRT1的表达增加，并激活重组SIRT1；而3-(2，4-二氯苯)-7-羟色酮和7-羟色酮仅诱导重组SIRT1激活；相反，染料木素、鹰嘴豆芽素、4，7-二甲氧基异黄酮和5，7，4-三甲氧基异黄酮仅增加肾小管上皮细胞中SIRT1的表达			1.提高PGC-1α的表达 2. ATP合酶β和泛醌氧化还原酶核心亚基6的表达增加 3.肾小管上皮细胞中基础呼吸增加至1.5倍和ATP合成量增加至1.9倍	[18]

药物名称	成分/机制	慢性肾脏病模型	肾脏疗效	反映线粒体生物合成的指标	参考文献
APX115	Nox抑制剂	STZ诱导DKD小鼠	1.减少蛋白尿 2.改善肾小球肥大、肾小管和足细胞损伤以及肾纤维化 3.减少肾脏脂质沉积、炎症、氧化应激	1. PGC-1α 2. NRF1、TFAM	[9]
葡萄籽原花青素提取物	多酚	STZ诱导DKD大鼠	1.改善系膜扩张、改善足突融合和基底膜增厚 2.减轻凋亡	SIRT1、PGC-1α、NRF1、TFAM	[10]
荔枝多酚	多酚	db/db小鼠(DKD)	改善系膜扩张、肾小球肥大	1. SIRT1、PGC-1α、NRF1、TFAM 2.呼吸链复合物亚基表达量	[11]
红景天苷	2-(4-羟基苯基)乙基β-D-吡喃葡萄糖苷	STZ诱导DKD小鼠	1.减少白蛋白尿；降低血清肌酐、血尿素氮 2.改善肾小球肥大、足突融合以及肾纤维化；减少纤维化蛋白表达(Col-Ⅰ、FN、α-SMA)	1. SIRT1、PGC-1α 2.呼吸链复合物亚基表达量 3. mtDNA含量	[12]
脂联素	血浆激素蛋白	STZ诱导DKD大鼠＋高糖刺激NRK-52E细胞	1.减少蛋白尿；降低血清肌酐、血尿素氮 2.改善系膜扩张、基底膜增厚	1. PGC-1α、TFAM 2.呼吸链复合物亚基表达量 3. mtDNA含量	[13]
萝卜硫素	异硫氰酸酯	UUO大鼠	减缓小管损伤、坏死；减少纤维化蛋白表达(α-SMA)	1.呼吸链复合物亚基表达量 2.线粒体数量的标志物VDAC和ANT密度分析	[14]
蒿甲醚		阿霉素肾病小鼠	1.降低尿蛋白/肌酐比 2.改善肾小管损伤、肾小管表型转变	NRF1、TFAM	[15]
绿茶多酚	有效活性成分包括表没食子儿茶素没食子酸酯(占比47.2%)等	环孢素肾病大鼠	1.降低血清肌酐 2.改善肾小管损伤、肾纤维化	1. PGC-1 α、TFAM 2.呼吸链复合物亚基表达量 3. mtDNA含量	[16]
水飞蓟素	至少6种主要的同分异构体黄酮类化合物和少量黄酮类化合物	高脂喂养小鼠＋HK细胞(棕榈酸刺激)	1.改善肾小球系膜扩张、胶原沉积 2.减少肾脏脂质沉积和活性氧自由基生成	1. PGC-1α、NRF2、TFAM 2.线粒体DNA含量	[17]
一系列异黄酮	大豆黄酮和刺芒柄花素诱导肾小管上皮细胞中SIRT1的表达增加，并激活重组SIRT1；而3-(2，4-二氯苯)-7-羟色酮和7-羟色酮仅诱导重组SIRT1激活；相反，染料木素、鹰嘴豆芽素、4，7-二甲氧基异黄酮和5，7，4-三甲氧基异黄酮仅增加肾小管上皮细胞中SIRT1的表达			1.提高PGC-1α的表达 2. ATP合酶β和泛醌氧化还原酶核心亚基6的表达增加 3.肾小管上皮细胞中基础呼吸增加至1.5倍和ATP合成量增加至1.9倍	[18]

药物名称	成分/机制	慢性肾脏病模型	肾脏疗效	反映线粒体生物能学的指标	参考文献
铈纳米颗粒	抗氧化剂	UUO小鼠＋TGF-β刺激肾小管上皮细胞系HK2细胞	改善肾脏纤维化；减少纤维化蛋白表达(Col-Ⅰ、FN、α-SMA)	1.提高基础和最大耗氧量；抑制无氧糖酵解，增强氧化磷酸化 2.改善肾脏氧化应激	[27]
辅酶Q10	内源性抗氧化剂	他克莫司诱导大鼠肾小管上皮细胞系HK2细胞(他克莫司刺激)	1.降低血清肌酐、血尿素氮 2.改善肾脏纤维化	1.提高基础和最大耗氧量 2.改善肾脏氧化应激	[28]
Bemcentinib	Axl-抑制剂	UUO小鼠	－	基因测序	[29]
氟非尼酮	TGF-β抑制剂	UUO小鼠＋ TGF-β刺激肾小管上皮细胞系HK2细胞	1.降低血清肌酐、血尿素氮 2.改善肾脏纤维化；减少纤维化蛋白表达(Col-I、Col-III、FN、α-SMA)	1.提高ATP产量 2.改善肾脏氧化应激	[30]

药物名称	成分/机制	慢性肾脏病模型	肾脏疗效	反映线粒体生物能学的指标	参考文献
铈纳米颗粒	抗氧化剂	UUO小鼠＋TGF-β刺激肾小管上皮细胞系HK2细胞	改善肾脏纤维化；减少纤维化蛋白表达(Col-Ⅰ、FN、α-SMA)	1.提高基础和最大耗氧量；抑制无氧糖酵解，增强氧化磷酸化 2.改善肾脏氧化应激	[27]
辅酶Q10	内源性抗氧化剂	他克莫司诱导大鼠肾小管上皮细胞系HK2细胞(他克莫司刺激)	1.降低血清肌酐、血尿素氮 2.改善肾脏纤维化	1.提高基础和最大耗氧量 2.改善肾脏氧化应激	[28]
Bemcentinib	Axl-抑制剂	UUO小鼠	－	基因测序	[29]
氟非尼酮	TGF-β抑制剂	UUO小鼠＋ TGF-β刺激肾小管上皮细胞系HK2细胞	1.降低血清肌酐、血尿素氮 2.改善肾脏纤维化；减少纤维化蛋白表达(Col-I、Col-III、FN、α-SMA)	1.提高ATP产量 2.改善肾脏氧化应激	[30]

药物名称	成分/机制	慢性肾脏病模型	肾脏疗效	反映线粒体动力学的指标	参考文献
SS31	线粒体靶向抗氧化剂	STZ诱导DKD小鼠＋高糖刺激HK-2细胞	1.减少蛋白尿 2.改善系膜扩张、肾小球损伤、小管间质纤维化	1. Drp1 2. Mfn1 3.线粒体形态	[41]
乙酰半胱氨酸	抗氧化剂	STZ诱导DKD比格犬	1.减少白蛋白尿 2.改善肾小球与肾小管损伤以及纤维化	1. Mfn2 2. Drp1、MFF 3. OPA1、Mfn1、Fis1	[42]
鳄鱼油	脂肪酸	自发糖尿病大鼠	1.升高血清肌酐、血尿素氮、蛋白尿 2.加重系膜扩张，间质炎症	1. Mfn2、p-Drp1 2.线粒体形态	[43]
利莫那班	大麻素受体1拮抗剂	慢性间歇性缺氧大鼠	减轻小管损伤	1. Fis1、Mfn1 2.线粒体形态	[44]
肾衰二号		5/6肾切除大鼠＋低氧刺激NRK-52E细胞	减少纤维化蛋白表达(FN、Col-Ⅰ、结缔组织生长因子、α-SMA)	p-Drp1、Mfn1、Mfn2	[45]
淫羊藿甙		5/6肾切除大鼠＋TGF-β刺激NRK-52E细胞	减少纤维化蛋白表达(Col-Ⅰ、Col-Ⅲ、α-SMA)	1. p-Drp1、Mfn1、Mfn2 2.线粒体形态	[46]
健脾益肾方		腺嘌呤喂养大鼠	1.降低血清肌酐、血尿素氮 2.改善小管损伤、肾纤维化；减少纤维化蛋白表达(FN、Col-Ⅳ)	1. Drp1、OPA1 2.线粒体形态	[47]
黄芪丹参汤		腺嘌呤喂养大鼠	1.降低血清肌酐、血尿素氮 2.改善小管损伤、肾纤维化；减少纤维化蛋白表达(FN、Col Ⅳ、α-SMA)	Drp1、Mid51、Mid49、Mfn2、OPA1	[48,49]
JQ1	BET蛋白抑制剂	UUO小鼠＋ TGF-β1刺激HK2细胞		Drp1、OPA1	[50]

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