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接受腹膜透析液治疗的C反应蛋白转基因小鼠的腹膜炎症和纤维化

Peritoneal inflammation and fibrosis in C-reactive protein transgenic mice undergoing peritoneal dialysis solution treatment.

作者信息

Poon Peter Yam-Kau, Lan Hui-Yao, Kwan Bonnie Ching-Ha, Huang Xiao-Ru, Chow Kai-Ming, Szeto Cheuk-Chun, Li Philip Kam-Tao

机构信息

Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

From Carol & Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China.

出版信息

Nephrology (Carlton). 2017 Feb;22(2):125-132. doi: 10.1111/nep.12741.

Abstract

AIM

C-reactive protein (CRP) is a mediator of systemic inflammation. Peritoneal dialysis (PD) is known to cause peritoneal inflammation and fibrosis. We compare the degree of peritoneal inflammation and fibrosis in wild-type (WT) and CRP-transgenic (Tg) mice after PD treatment.

METHODS

WT (n = 7) and CRP-Tg (n = 10) C57BL/6 J mice (all male, 10-12 weeks old) were injected intra-peritoneally with 4.25% dextrose PD solution (3 mL/mouse) daily for 28 days, followed by a 2-h peritoneal equilibration test (PET). The mice were then killed. Parietal peritoneal and omental tissues were collected for the assessment of inflammation and fibrosis.

RESULTS

After 28 days of PD treatment, CRP-Tg mice had higher dialysate-to-plasma (D/P) creatinine ratio than that of WT mice. Parietal peritoneum of the CRP-Tg mice was more cellular and thicker than that of the WT mice. CRP-Tg mice also had higher connective tissue growth factor (CTGF), intercellular adhesion molecule 1 (ICAM1) and tumor necrosis factor α (TNFα) RNA expressions as well as immunohistochemical staining in the parietal peritoneum than that of the WT mice.

CONCLUSIONS

CRP-Tg mice have significantly more inflammation and fibrosis than WT mice after PD treatment. Our results suggest that CRP play a role in inflammation and fibrosis induced by PD. The implication of our results to human PD therapy needs further investigations.

摘要

目的

C反应蛋白(CRP)是全身炎症的介质。已知腹膜透析(PD)会导致腹膜炎症和纤维化。我们比较了野生型(WT)和CRP转基因(Tg)小鼠在接受PD治疗后的腹膜炎症和纤维化程度。

方法

将WT(n = 7)和CRP-Tg(n = 10)C57BL/6 J小鼠(均为雄性,10 - 12周龄)每天腹腔注射4.25%葡萄糖腹膜透析液(3 mL/小鼠),持续28天,随后进行2小时的腹膜平衡试验(PET)。然后处死小鼠。收集壁层腹膜和网膜组织以评估炎症和纤维化。

结果

PD治疗28天后,CRP-Tg小鼠的透析液与血浆(D/P)肌酐比值高于WT小鼠。CRP-Tg小鼠的壁层腹膜比WT小鼠的细胞更多且更厚。CRP-Tg小鼠壁层腹膜中的结缔组织生长因子(CTGF)、细胞间黏附分子1(ICAM1)和肿瘤坏死因子α(TNFα)的RNA表达以及免疫组化染色也高于WT小鼠。

结论

PD治疗后,CRP-Tg小鼠的炎症和纤维化明显多于WT小鼠。我们的结果表明CRP在PD诱导的炎症和纤维化中起作用。我们的结果对人类PD治疗的意义需要进一步研究。

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