摘要: |
目的 评估CNA35胶原靶向氟碳纳米粒(PFP-NPs)对糖尿病肾病(DN)肾脏纤维化的超声分子显像能力。方法 制备非靶向标记荧光的(非靶向)PFP-NPs和CNA35胶原靶向的荧光标记(靶向)PFP-NPs。TGF-β诱导人肾小管上皮细胞HK-2间质转化,分别使用非靶向PFP-NPs和靶向PFP-NPs与细胞进行共孵育,荧光显微镜下观察细胞荧光信号。建立DN大鼠模型,分别给予模型大鼠静脉注射非靶向PFP-NPs和靶向PFP-NPs,取肾脏组织,检测肾脏组织PFP-NPs及I型胶原荧光信号。采用超声分子成像技术检测肾纤维化成像情况;免疫组织化学分析肾脏组织I型胶原表达水平,分析肾脏超声分子成像信号强度与I型胶原水平相关性。结果 靶向PFP-NPs孵育的HK-2上的荧光信号显著强于非靶向PFP-NPs孵育的细胞(P<0.05)。靶向组DN大鼠肾脏组织PFP-NPs荧光信号显著强于非靶向组(P<0.05),且PFP-NPs荧光信号与I型胶原荧光信号区域重合;超声分子成像显示注射靶向PFP-NPs的大鼠肾脏信号强度显著高于注射非靶向PFP-NPs的大鼠(P<0.05);Pearson相关性分析显示大鼠肾脏I型胶原分布面积百分比与肾脏超声分子成像信号强度呈正相关。结论 CNA35靶向PFP-NPs能够靶向结合肾脏高表达胶原部位,实现了对DN的靶向超声分子显像。 |
关键词: CNA35 氟碳纳米粒 超声分子显像 肾纤维化 糖尿病肾病 |
DOI: |
投稿时间:2023-04-19修订日期:2023-05-03 |
基金项目:2022年河北省自然科学基金精准医学联合基金培育项目 |
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Study on the effect of CNA35 targeted perfluoropentane nanoparticles on ultrasonic molecular imaging of renal fibrosis in diabetic nephropathy |
Feng Yujin,Yang Xiaoyun,Zhao Kun,Liu Fen,Zong Meinan,wangyi |
(The Second Hospital of Hebei Medical University) |
Abstract: |
Objective To evaluate the ultrasonic molecular imaging ability of CNA35 targeted perfluoropentane nanoparticles (PFP-NPs) for renal fibrosis in diabetic nephropathy. Methods Preparation of non-targeted fluorescent labeled (non-targeted) PFP-NPs and CNA35 collagen-targeted fluorescent labeled (targeted) PFP-NPs. TGF-β induced interstitial transformation of human renal tubular epithelial cells HK-2. The cells were co-incubated with non-targeted PFP-NPs and targeted PFP-NPs, and the fluorescence signal of the cells was observed under a fluorescence microscope. The DN rat model was established, and the model rats were given intravenous injection of non-targeted PFP-NPs and targeted PFP-NPs, respectively. The kidney tissue was taken to detect the fluorescence signals of PFP-NPs and type I collagen in the kidney tissue. Ultrasound molecular imaging was used to detect renal fibrosis imaging. The expression level of type I collagen in renal tissue was analyzed by immunohistochemistry, and the correlation between the signal intensity of renal ultrasound molecular imaging and the level of type I collagen was analyzed. Results The fluorescence signal of HK-2 incubated with targeted PFP-NPs was significantly stronger than that of cells incubated with non-targeted PFP-NPs (P < 0.05). The fluorescence signal of PFP-NPs in the kidney tissue of DN rats in the targeted group was significantly stronger than that in the non-targeted group (P < 0.05), and the fluorescence signal of PFP-NPs coincided with the fluorescence signal area of type I collagen. Ultrasound molecular imaging showed that the renal signal intensity of rats injected with targeted PFP-NPs was significantly higher than that of rats injected with non-targeted PFP-NPs (P < 0.05). Pearson correlation analysis showed that the percentage of type I collagen distribution area in rat kidney was positively correlated with the signal intensity of renal ultrasound molecular imaging. Conclusion CNA35 targeted PFP-NPs can target the high expression of collagen in the kidney, and achieve targeted ultrasound molecular imaging of diabetic nephropathy. |
Key words: CNA35 fluorocarbon nanoparticles ultrasonic molecular imaging renal fibrosis diabetic nephropathy |