In Vivo Quantitative Visualization Analysis of the Effect of C-Peptide on Glomerular Hyperfiltration in Diabetic Rats by Using Multiphoton Microscopy
In Vivo Quantitative Visualization Analysis of the Effect of C-Peptide on Glomerular Hyperfiltration in Diabetic Rats by Using Multiphoton Microscopy
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DOI：
10.1111/micc.12043
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发表时间：
2013-07-01
期刊：
影响因子：
2.4
通讯作者：
Kajiya, Fumihiko
中科院分区：
文献类型：
--
作者：
Nakamoto, Hiroshi;Kajiya, Fumihiko
目的：本研究的目的是在体内条件下观察糖尿病早期大鼠肾小球高滤过，并定量检测C肽对滤过的影响。方法：用链脲佐菌素(50mg/kg)诱导Wistar大鼠1型糖尿病。将大鼠分为四组：对照组、对照组加C肽、早期糖尿病组、早期糖尿病加C肽组。连续输注C肽（50pmol/kg/min）。通过与德克萨斯红缀合的各种大小的葡聚糖（3k至70kDa）的团注来可视化过滤，并在吸入麻醉下用多光子显微镜观察。相对筛分系数用于量化过滤。结果：在对照大鼠和糖尿病大鼠中几乎所有较小颗粒（3-10kDa）都被过滤。在正常大鼠中观察到较大颗粒（40-70kDa）的过滤，但在糖尿病大鼠中更为明显，并且根据糖尿病的持续时间进行进展。 C 肽给药将较大颗粒的渗漏恢复至对照水平。结论：我们对超滤进行可视化和分析，并证实 C 肽具有肾保护作用。此外，我们发现随着糖尿病病程的延长，较大颗粒的渗漏也会增加。
Objective: The purpose of this study was to visualize glomerular hyperfiltration in rats at the early stage of diabetes under in vivo conditions and to quantitatively examine the effect of C-peptide on filtration.Methods: Type 1 diabetes was induced by streptozotocin (50mg/kg) in Wistar rats. The rats were divided into four groups: control, control plus C-peptide, early diabetes, and early diabetes plus C-peptide. C-peptide was continuously infused (50pmol/kg/min). Filtration was visualized by a bolus shot of various sizes of dextrans (3k to 70kDa) conjugated with Texas Red and observed with a multiphoton microscope under inhaled anesthesia. Relative sieving coefficients were used to quantify filtration.Results: Almost all smaller particles (3-10kDa) were filtered both in control and diabetic rats. Filtration of larger particles (40-70kDa) was seen in normal rats but was more apparent in diabetic rats, where it was progressive according to the duration of diabetes. C-peptide administration restored the leakage of larger particles to the level seen for the control.Conclusions: We visualized and analyzed hyperfiltration and confirmed that C-peptide has a nephroprotective effect. Furthermore, we found that the leakage of larger particles increased as the duration of diabetes increased.