Leibowitz Avshalom, Volkov Alexander, Voloshin Konstantin, Shemesh Chen, Barshack Iris, Grossman Ehud
Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
J Pineal Res. 2016 Jan;60(1):48-54. doi: 10.1111/jpi.12287. Epub 2015 Nov 18.
Melatonin, a potent antioxidant molecule, plays a role in blood pressure regulation. We hypothesized that melatonin may generate a protective effect in a high salt diet (HSD) rodent model mediated by decreasing renal oxidative stress. Dahl salt-sensitive rats were divided into three groups according to diet: normal chow (control); HSD; HSD with melatonin [30/mg/kg/day]) placed in their water (HSD + Mel) over an 8-wk period. Blood pressure was measured by the tail cuff method. Kidney injury was evaluated by 24 H urine protein excretion. Glomerular injury index (GII) (fibrotic glomeruli/100 glomeruli) was evaluated from a Masson's trichrome-stained section. Kidney oxidative stress was determined by superoxide production via dihydroethidium staining. Expression of oxidative stress-related genes was measured by reverse transcriptase-qPCR. Melatonin had no effect on blood pressure increase induced by HSD and attenuated proteinuria induced by HSD (HSD--50.7 ± 12, HSD + Mel--22.3 ± 4.3, controls--6.5 ± 1.0 gram protein/gram creatinine, P < 0.001). HSD-induced glomerular damage was significantly diminished by melatonin (GII in HSD--24 ± 6, HSD + Mel--3.6 ± 0.8, controls--0.8 ± 0.5, P < 0.05). Superoxide production was significantly higher in kidneys of HSD fed rats than the controls (99 ± 9 versus 60 ± 7 relative fluorescent units (RFU)/μm(2), respectively, P < 0.05). Melatonin also decreased superoxide production (74 ± 5 RFU/μm(2), P < 0.05). The expression of kidney inducible nitric oxide synthase and p67(phox) mRNA was significantly higher in HSD than in the controls and HSD + Mel rats. Treatment with melatonin eliminated the deleterious effect of HSD in the kidneys of Dahl salt-sensitive rats. The beneficial effect of melatonin is not mediated by lowering blood pressure but by a direct antioxidative effect.
褪黑素是一种强效抗氧化分子，在血压调节中发挥作用。我们假设褪黑素可能通过降低肾脏氧化应激，在高盐饮食（HSD）啮齿动物模型中产生保护作用。将 Dahl 盐敏感大鼠根据饮食分为三组：正常饲料（对照组）；高盐饮食组；高盐饮食并在饮水中添加褪黑素[30毫克/千克/天]（HSD + Mel），为期8周。通过尾袖法测量血压。通过24小时尿蛋白排泄评估肾脏损伤。从 Masson三色染色切片评估肾小球损伤指数（GII）（纤维化肾小球/100个肾小球）。通过二氢乙锭染色法测定肾脏超氧化物生成量来确定肾脏氧化应激。通过逆转录定量PCR测量氧化应激相关基因的表达。褪黑素对高盐饮食诱导的血压升高没有影响，但可减轻高盐饮食诱导的蛋白尿（HSD组为50.7±12，HSD + Mel组为22.3±4.3，对照组为6.5±1.0克蛋白质/克肌酐，P<0.001）。褪黑素显著减轻了高盐饮食诱导的肾小球损伤（HSD组的GII为24±6，HSD + Mel组为3.6±0.8，对照组为0.8±0.5，P<0.05）。高盐饮食喂养大鼠的肾脏中超氧化物生成量显著高于对照组（分别为99±9和60±7相对荧光单位（RFU）/μm²，P<0.05）。褪黑素也降低了超氧化物生成量（74±5 RFU/μm²，P<0.05）。高盐饮食组大鼠肾脏中诱导型一氧化氮合酶和p67(phox) mRNA的表达显著高于对照组和HSD + Mel组大鼠。褪黑素治疗消除了高盐饮食对 Dahl 盐敏感大鼠肾脏的有害影响。褪黑素的有益作用不是通过降低血压介导的，而是通过直接的抗氧化作用。
