title: Zhi-Long-Huo-Xue-Tong-Yu modulates mitochondrial fission through the ROCK1 pathway in mitochondrial dysfunction caused by streptozotocin-induced diabetic kidney injury.
abstract: Zhi-Long-Huo-Xue-Tong-Yu (ZLHXTY) is a defined mixture of 5 herbs developed by Professor S.J. Yang according to the Buyang Huanwu decoction method, which has been recorded in the Yilingaicuo. This study investigated the renoprotective effects of ZLHXTY on mitochondrial dysfunction induced by diabetic kidney injury in a diabetic rat model. Diabetes was induced by a single intravenous injection of streptozotocin. Rats were daily fed either ZLHXTY or vehicle beginning in the 1st week after injection. Levels of mitofusin 2 (mfn2), dynamin-related protein 1 (Drp1), caspase-9, and rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) were detected using Western blotting. Levels of intracellular calcium and adenosine triphosphate (ATP) were examined using an enzyme-linked immunosorbent assay. An electron microscopic examination of kidney tissue was performed. The levels of mfn2 and ATP in the diabetes and ZLHXTY groups decreased from the 4th week after modeling. The expression levels of Drp1, ROCK1, and caspase-9 increased in the diabetes group but decreased in the ZLHXTY group from the 4th week after modeling. Compared with the diabetes group, ZLHXTY treatment decreased the mesangial expansion index and proteinuria levels, and improved the pathological changes typical of diabetic kidney injury. Furthermore, ZLHXTY treatment inhibited the activation of ROCK1 and expression of Drp1 and caspase-9, but did not affect the expression of mfn2. This study indicates that ZLHXTY treatment could protect kidney tissue from diabetic injury through the ROCK1 pathway response to mitochondrial dysfunction induced by diabetes.
authors.affiliation: Department of Nephropathy, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: W H
authors.initials: WH
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Traditional Chinese Medical Hospital, Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: M P
authors.initials: MP
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Traditional Chinese Medical Hospital, Luzhou Medical College, Luzhou, Sichuan, China whhhwei@126.com.
authors.forename: S J
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Department of Nephropathy, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Traditional Chinese Medical Hospital, Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: X
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Nephropathy, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: J H
authors.initials: JH
authors.lastname: Qin
authors.affiliation: Department of Nephropathy, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: B
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Nephropathy, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: S T
authors.initials: ST
authors.lastname: Ou
authors.affiliation: Department of Nephropathy, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Traditional Chinese Medical Hospital, Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, Traditional Chinese Medical Hospital, Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Traditional Chinese Medical Hospital, Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: Q D
authors.initials: QD
authors.lastname: Hu
authors.affiliation: Department of Urology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: L
authors.initials: L
authors.lastname: Xue
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; C578418:ROCK1 protein, rat; D054460:rho-Associated Kinases; D053453:Caspase 9; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat; C519851:Dnm1l protein, rat; D034281:Dynamins; D002118:Calcium