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目的观察川芎嗪对高糖致大鼠腹膜间皮细胞MCP-1与NF-κB p65表达的影响,探讨其在持续性不卧床腹膜透析(continuous ambulatory peritoneal dialysis,CAPD)时腹膜慢性炎症发病机制中的可能作用。方法 60只健康雄性SD大鼠按随机数字表法分成3组:对照组(n=20):腹腔每天注射生理盐水25 mL;模型组(n=20,HGC组):腹腔每天注射4.25%葡萄糖腹透液25 mL+每周1次腹腔注射红霉素6.25万单位;治疗组(n=20,HGM组):腹腔每天注射4.25%葡萄糖腹透液25 mL+2%川芎嗪溶液(40 mg/L)+每周1次腹腔注射红霉素6.25万单位。8周后分别处死各组大鼠,取腹膜组织以SABC免疫组织化学法检测壁腹膜间皮细胞MCP-1、NF-κB p65的表达,并行腹膜组织HE及Masson染色病理学检查。结果与对照组比较,HGC组和HGM组腹膜间皮细胞MCP-1[(109.69±5.33),(122.46±5.00)与NF-κB p65(104.83±2.31),(116.44±5.55)表达上调(P<0.05)],且HGC组显著高于HGM组(P<0.05)。大鼠腹膜间皮细胞MCP-1与NF-κB p65表达水平成正相关(r=0.81,P<0.05)。HE染色后光镜下HGC组和HGM组可见腹膜间皮细胞由扁平变为圆形、柱形,间皮细胞肥大脱落,间皮下结缔组织明显增厚,可见血管生成以及纤维素样物质沉积,还可见成纤维细胞及单核巨噬细胞浸润,HGC组表现尤为明显。结论川芎嗪可能拮抗高糖引起的腹膜间皮细胞MCP-1与NF-κBp65表达,从而减轻腹膜慢性炎症,延缓腹膜纤维化的发生。
Objective To investigate the effects of ligustrazine on the expression of MCP-1 and NF-κB p65 in rat peritoneal mesothelial cells induced by high glucose, and to explore the role of ligustrazine in the pathogenesis of chronic peritoneal inflammation in continuous ambulatory peritoneal dialysis (CAPD) The possible role. Methods Sixty male Sprague-Dawley rats were randomly divided into three groups according to the random number table: control group (n = 20): intraperitoneal injection of normal saline 25 mL per day; model group (n = 20, HGC group): intraperitoneal injection of 4.25% glucose (N = 20, HGM group): intraperitoneal injection of 4.25% glucose peritoneal solution 25 mL + 2% tetramethylpyrazine solution (40 mg / L) + weekly intraperitoneal injection of 6.25 million units of erythromycin. After 8 weeks, the rats in each group were sacrificed, and the peritoneal tissues were harvested for immunohistochemical staining for MCP-1 and NF-κB p65 expression in the peritoneal mesothelial cells. Peritoneal tissue HE and Masson staining were used for pathological examination. Results Compared with the control group, the expressions of MCP-1 [(109.69 ± 5.33), (122.46 ± 5.00) and NF-κB p65 (104.83 ± 2.31) and (116.44 ± 5.55) in HGC and HGM groups were significantly increased <0.05)], and the HGC group was significantly higher than the HGM group (P <0.05). The expression of MCP-1 in rat peritoneal mesothelial cells positively correlated with the expression of NF-κB p65 (r = 0.81, P <0.05). HGC group and HGM group under light microscopy showed that peritoneal mesothelial cells changed from flattened to round, the columnar and mesothelial cells became hypertrophy, and the connective tissue in the mesothelium was obviously thickened. The angiogenesis and deposition of cellulose-like substance were observed, Also visible fibroblasts and monocyte-macrophage infiltration, HGC group was particularly evident. Conclusion Ligustrazine can antagonize high glucose-induced expression of MCP-1 and NF-κBp65 in peritoneal mesothelial cells, thereby reducing peritoneal chronic inflammation and delay the occurrence of peritoneal fibrosis.