摘要
目的观察褪黑素(melatonin,MT)对大鼠腹膜透析相关性腹膜纤维化的影响。方法将38只雄性SD大鼠分为对照组(6只)、腹膜纤维化模型组(8只)、模型+低剂量MT(5mg·kg^(-1)·d^(-1))腹腔给药组(8只)、模型+中剂量MT(10mg·kg^(-1)·d^(-1))腹腔给药组(8只)、模型+高剂量MT(20 mg·kg^(-1)·d^(-1))腹腔给药组(8只)。腹腔注射4.25%腹膜透析液100 ml·kg^(-1)·d^(-1)建立腹膜纤维化大鼠模型。实验第28天行4h腹膜平衡实验(peritoneal equilibration test,PET),量取超滤量(ultrafiltration,UF),检测腹透液尿素氮浓度(dialysate urea nitrogen concentration,D)、血浆尿素氮浓度(plasma urea nitrogen concentration,Purea)、初始腹膜透析液葡萄糖浓度(D0)、4 h后透出液葡萄糖浓度(D4),并计算D/Purea、D4/D0。取大鼠壁层腹膜组织行HE和Masson染色,采用免疫组化方法检测转化生长因子β1(transforming growth factorβ1,TGF-β1),胶原Ⅰ(collagenⅠ,Col-Ⅰ)和α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)表达。结果 4 h PET显示模型组与对照组相比,UF和D4/D0明显减少(P<0.05),D/Purea明显增加(P<0.05);MT各给药组与模型组比较,UF和D4/D0明显增加(P<0.05),D/Purea明显减少(P<0.05);HE和Masson染色显示对照组腹膜菲薄,间皮细胞连接紧密,模型组腹膜明显增厚,部分可见间皮细胞缺失,间皮下可见胶原沉积,MT各给药组上述腹膜病理改变较模型组明显减轻;免疫组化显示模型组TGF-β1、Col-Ⅰ、α-SMA表达明显高于对照组(P<0.05),MT各给药组表达明显低于模型组(P<0.05)。结论 MT能通过改善腹膜的结构和功能来发挥其对抗大鼠腹膜纤维化的作用并能抑制TGF-β1、Col-Ⅰ和α-SMA表达。
Objective To investigate the effects of melatonin （MT） on peritoneal fibrosis in- duced by high glucose peritoneal dialysis in rats. Methods 38 SD male rats were randomly assigned into 5 groups： control group （n = 6）, peritoneal fibrosis group （n = 8）, peritoneal fibrosis ＋ MT 5 mg·kg^-1·d^-1 administration group （low MT dose group, n=8）, peritoneal fibrosis ＋ MT 10 mg·kg^-1·d^-1 administration group （moderate MT dose group, n= 8）, peritoneal fibrosis ＋ MT 20 mg·kg^-1·d^-1 administration group （high MT dose group, n = 8）. The rats were injected intraperitoneal with 4. 25% peritoneal dialysis fluid at 100 ml·kg^-1 daily to build peritoneal fibrosis model. After 28 days, 4 h peritoneal equilibration test （PET） was carried out, measuring amount of ultrafiltration （UF）, and calculating both dialysate-to-plasma ratios （D/P） for creatinine at 4 b and the ratio of glucose at 4 h to the dialysate glucose concentration at time zero （D/D0）. Rats were killed, taking the parietal peritoneum HE and Masson staining to observe the morphological changes of the peritoneum. We use immunohistochemical methods to detect the expressions of transforming growth factor β1 （TGF-β1）, collagen I （Col-Ⅰ） and a-smooth muscle aetin （α-SMA）. Results （1） Compared with the control group, UF and D4/D0 were significantly decreased （P〈0. 05） and D/Purea was markedly increased （P〈0. 05） in model group; Compared with the model group, UF and D4/D0 were significantly in- creased （P〈0. 05） and D/Purea was markedly decreased （P〈0.05） in MT groups. （2） In the control group, the peritoneal tissues had smooth surface, the visible flat mesothelial monolayer cells covered loose connective tissues; compared with the control group, the peritonea of the model group were markedly thickened, with rough surface, and mesothelial cells were swelling and lost with collagen deposition. All above mentioned pathological changes reduced markedly in MT groups. （3） Ex
出处
《临床肾脏病杂志》
2016年第4期240-245,共6页
Journal Of Clinical Nephrology
基金
安徽省自然科学基金(NO.1408085MH183)
