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代谢综合征相关肾结石形成因素的初步动力学分析:大鼠模型中的证据。

A pilot dynamic analysis of formative factors of nephrolithiasis related to metabolic syndrome: evidence in a rat model.

机构信息

Department of Urology, Key Laboratory of Disease of Urological Systems, Gansu Nephro-Urological Clinical Center, Lanzhou University Second Hospital, Lanzhou, China.

College of Animal Science and Technology, Guangxi University, Nanning, China.

出版信息

Ren Fail. 2022 Dec;44(1):1134-1143. doi: 10.1080/0886022X.2022.2097922.

DOI:10.1080/0886022X.2022.2097922
PMID:35837686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9291672/
Abstract

INTRODUCTION AND OBJECTIVE

To examine the dynamic changes in the formative factors of nephrolithiasis and the final micromorphological changes in an obesity-initiated metabolic syndrome (MS) rat model.

METHODS

Forty five-week-old male Sprague-Dawley (SD) rats were randomly divided into four groups: the regular diet group (RD), high-fat diet group (HFD), regular diet with drug (ethylene glycol and ammonium chloride) group (RDD), and high-fat diet with drug group (HFDD). A dynamic assessment of MS components (body weight (BW), body length (BL), Lee's index (LI), blood glucose (BG), total cholesterol (TC), and triglycerides (TGs)) and stone-forming factors (urinary pH, urinary calcium, and urinary oxalate acid) was carried out. In addition, the levels of oxidative stress (OS) markers (CAT, SOD, TAC, GSH-PX, and MDA) were measured, and histological analysis was carried out at the end of 16 weeks.

RESULTS

MS-related parameters, such as BW, LI, BG, TC, and TG, were significantly higher in HFD-fed rats than in RD-fed rats ( < 0.001). In the HFDD group, significantly lower urinary pH, hyperoxaluria, and hypocalciuria were noted in the dynamic assessment of stone-forming factors ( < 0.001). CAT, TAC, and MDA were notably changed in the HFD-fed groups, particularly the HFDD rats. Histological analysis showed that the renal tubules of HFDD rats had the highest scores for both inflammation and renal crystallization deposition ( < 0.05).

CONCLUSIONS

Our results suggest that male SD rats with MS are prone to developing nephrolithiasis. Validation in an model may lead to an understanding of the underlying pathophysiological mechanisms of action of MS-related nephrolithiasis in humans.Key messagesMale SD rats with metabolic syndrome are more prone to developing calcium oxalate nephrolithiasis after treatment with ethylene glycol and ammonium chloride compared to control lean rats.MS-related nephrolithiasis in rats induced by ethylene glycol and ammonium chloride is mainly related to increased hyperoxaluria and inflammation and decreased antioxidant levels.High-fat diet-fed SD rats treated with ethylene glycol and ammonium chloride are a stable and valid model for understanding the potential mechanism of action of MS-related nephrolithiasis.

摘要

简介和目的

研究肥胖诱发的代谢综合征(MS)大鼠模型中肾结石形成因素的动态变化和最终的微观形态变化。

方法

将 45 周龄雄性 Sprague-Dawley(SD)大鼠随机分为四组:普通饮食组(RD)、高脂饮食组(HFD)、普通饮食加药物(乙二醇和氯化铵)组(RDD)和高脂饮食加药物组(HFDD)。对 MS 成分(体重(BW)、体长(BL)、Lee 指数(LI)、血糖(BG)、总胆固醇(TC)和甘油三酯(TGs))和结石形成因素(尿 pH 值、尿钙和尿草酸)进行动态评估。此外,在 16 周结束时测量氧化应激(OS)标志物(CAT、SOD、TAC、GSH-PX 和 MDA)的水平,并进行组织学分析。

结果

与 RD 喂养的大鼠相比,HFD 喂养的大鼠的 MS 相关参数(BW、LI、BG、TC 和 TG)显著升高(<0.001)。在 HFDD 组中,结石形成因素的动态评估中,尿 pH 值明显降低、高草酸尿症和低钙尿症明显(<0.001)。CAT、TAC 和 MDA 在 HFD 喂养的大鼠中明显改变,特别是 HFDD 大鼠。组织学分析显示,HFDD 大鼠的肾小管炎症和肾结晶沉积评分最高(<0.05)。

结论

我们的结果表明,患有 MS 的雄性 SD 大鼠更容易发生肾结石。在模型中验证可能会导致人们对与 MS 相关的肾结石的潜在病理生理机制有更深入的了解。

关键信息

与对照瘦大鼠相比,用乙二醇和氯化铵治疗后,患有代谢综合征的雄性 SD 大鼠更容易发生草酸钙肾结石。

大鼠代谢综合征相关肾结石的形成主要与高草酸尿症、炎症增加和抗氧化水平降低有关。

用乙二醇和氯化铵治疗的高脂肪饮食喂养的 SD 大鼠是一种稳定有效的模型,可用于了解与 MS 相关的肾结石形成的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/ac93fdb5c2a4/IRNF_A_2097922_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/bff4b6cffa64/IRNF_A_2097922_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/27cee17c7ae9/IRNF_A_2097922_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/eb9769b47295/IRNF_A_2097922_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/3f4a551966e1/IRNF_A_2097922_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/b305ed47c0d7/IRNF_A_2097922_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/ac93fdb5c2a4/IRNF_A_2097922_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/bff4b6cffa64/IRNF_A_2097922_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/27cee17c7ae9/IRNF_A_2097922_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/eb9769b47295/IRNF_A_2097922_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/3f4a551966e1/IRNF_A_2097922_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/b305ed47c0d7/IRNF_A_2097922_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cab/9291672/ac93fdb5c2a4/IRNF_A_2097922_F0006_C.jpg

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和提取物及卡维地洛对乙二醇诱导的尿石症的肾保护作用:NF-κB、p53、Bcl-2、Bax 和 Bak 的作用。
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Rosiglitazone Suppresses Calcium Oxalate Crystal Binding and Oxalate-Induced Oxidative Stress in Renal Epithelial Cells by Promoting PPAR- Activation and Subsequent Regulation of TGF-1 and HGF Expression.罗格列酮通过促进 PPAR 激活及随后对 TGF-β1 和 HGF 表达的调节,抑制草酸钙晶体结合和草酸诱导的肾小管上皮细胞氧化应激。
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