目的 研究腹膜透析液的钙离子浓度对腹膜透析患者腹膜纤维化、上皮间质转化(epithelial mesenchymal transition，EMT)及内质网应激(endoplasmic reticulum stress，ERS)的影响。 方法 选择使用标准钙腹膜透析液进行持续性非卧床腹膜透析的患者进行随机对照研究，分为观察组(改用低钙腹膜透析液)和对照组(继续使用标准钙腹膜透析液)，设置入组时为0月、试验结束时为6月。记录入组时的临床资料，收集0月和6月时的透出液并检测转化生长因子-β1(transforming growth factors-β1，TGF-β1)、纤维连接蛋白(fibronectin，FN)、胶原蛋白-I(collagen-I，Col-I)的含量及E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、紧密连接蛋白-1(zonula occluden-1，ZO-1)、α-平滑肌肌动蛋白(α-smooth muscle actin，α-SMA)、CCAAT增强子结合蛋白同源蛋白(CCAAT enhancer binding protein homologous protein，CHOP)、磷酸化蛋白激酶R样内质网激酶(phosphorylated protein kinase R-like endoplasmic reticulum kinase，p-PERK)、磷酸化真核翻译起始因子2α(phosphorylated eukaryotic translation initiation factor 2 α，p-eIF2α)、转录激活因子4(activating transcription factor 4，ATF4)的表达水平。 结果 共纳入49例患者，其中观察组24例、对照组25例。经过6个月治疗，观察组透出液中TGF-β1、FN、Col-I的含量及α-SMA、N-cadherin、p-PERK、 p-eIF2α、ATF4、CHOP的表达水平均低于对照组(t值分别为4.599、2.161、6.557、9.357、8.565、8.634、7.518、8.842、10.989，P值分别为＜0.001、0.036、＜0.001、＜0.001、＜0.001、＜0.001、＜0.001、 ＜0.001、＜0.001)，E-cadherin、ZO-1的表达水平均高于对照组(t=16.684、22.273，均P＜0.001)。 结论 低钙透析液能够减轻腹膜透析患者的腹膜纤维化及EMT，EMT及ERS可能是与之相关的分子机制。
Objective To study the effect of calcium ion concentration in peritoneal dialysate on peritoneal fibrosis, epithelial mesenchymal transition (EMT) and endoplasmic reticulum stress (ERS) of peritoneal dialysis patients. Method A randomized controlled study was conducted on patients who underwent continuous non-bedridden peritoneal dialysis using standard calcium peritoneal dialysate. They were divided into low calcium group and control group. Patients in low calcium group switched to low calcium peritoneal dialysate while those in the control group continued to use the peritoneal dialysate with standard calcium concentration. The enrollment time point was set at 0 month and the end of the experiment was set after 6 months. Their clinical data at the time of enrollment were recorded. The outflow dialysates at 0 and 6 months were collected to measure the contents of transforming growth factors-β1 (TGF-β1), fibronectin (FN) and collagen-I (Col-I), and the expression levels of E-cadherin, N-cadherin, ZO-1, α-smooth muscle actin (α-SMA), CCAAT enhancer binding protein homologous protein (CHOP), phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2 α (p-eIF2α) and transcription activating factor 4 (ATF4). Results A total of 49 patients were enrolled, including 24 in low calcium group and 25 in control group. After 6 months of treatment, the contents of TGF-β1, FN, Col-I and the expression levels of α-SMA, N-cadherin, p-PERK, p-eIF2α, ATF4 and CHOP were lower in low calcium group than in control group (t=4.599, 2.161, 6.557, 9.357, 8.565, 8.634, 7.518, 8.842 and 10.989 respectively; P＜0.001, =0.036, ＜0.001, ＜0.001, ＜0.001, ＜0.001, ＜0.001, ＜0.001 and ＜0.001 respectively), while the expression levels of E-cadherin and ZO-1were higher in low calcium group than in control group (t=16.684 and 22.273; P＜0.001 and＜0.001). Conclusion Low calcium dialysate can alleviate peritoneal fibrosis, of which the molecular mechanism may relate to the inhibition of EMT and ERS by low calcium dialysate.
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