Poon Peter Yam-Kau, Lan Hui-Yao, Kwan Bonnie Ching-Ha, Huang Xiao-Ru, Chow Kai-Ming, Szeto Cheuk-Chun, Li Philip Kam-Tao
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.
Nephrology (Carlton). 2017 Feb;22(2):125-132. doi: 10.1111/nep.12741.
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.
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.
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.
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.
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。
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。
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。
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。