肝素联合柴胡对内毒素诱导大鼠肾损伤的保护作用

Protective effect of heparin combined with Bupleurum on renal injury in endotoxin-induced rats

目的观察肝素联合柴胡注射液对内毒素诱导大鼠肾脏损伤的保护作用。方法选取健康SD大鼠共18只,利用腹腔注射7 mg/kg脂多糖(LPS)诱导建立内毒素大鼠肾损伤模型;采用随机数表法将造模后的大鼠随机分为模型组、肝素组和肝素+柴胡组,每组6只。肝素组腹腔注射120 U/kg低分子肝素,肝素+柴胡组给予120 U/kg低分子肝素与200 mg/kg柴胡注射液;另选健康SD大鼠8只作为对照组,给予同剂量生理盐水。药物处理后5 h取血,利用生化仪检测肌酐(CRE)浓度,采用血凝仪测定活化部分凝血活酶时间(APTT)和纤维蛋白原(FIB)含量,显微镜下观察肾脏组织病理学改变。结果与对照组比较,模型组大鼠的CRE浓度[(76.95±12.05)μmol/L vs(47.00±5.55)μmol/L]显著升高、APTT时间[(53.80±19.37)s vs(19.70±3.25)s]显著延长,FIB含量[(53.17±12.95)mg/dL vs(440.89±44.64)mg/dL]显著降低,差异均有显著统计学意义(P<0.01);显微镜下模型组大鼠肾小球结构萎缩,肾间质血管弥漫性扩张充血;与模型组比较,肝素组大鼠的APTT时间[(32.77±1.86)s vs(53.80±19.37)s]缩短、FIB含量[(399.01±56.66)mg/dL vs(53.17±12.95)mg/dL]回升,差异均有统计学意义(P<0.05);CRE浓度虽有所降低,但差异无统计学意义(P>0.05)。与模型相比,肝素+柴胡组大鼠的CRE浓度[(52.53±13.14)μmol/L vs(76.95±12.05)μmol/L]、APTT时间[(21.73±0.72)s vs(53.80±19.37)s]、FIB含量[(368.50±41.32)mg/dL vs(53.17±12.95)mg/dL]均明显改善,差异有统计学意义(P<0.05);镜下肝素+柴胡组大鼠肾小球结构基本恢复正常,肾间质充血明显减轻。结论单纯肝素抗凝治疗不足以逆转内毒素所致的肾损伤,肝素联合柴胡对内毒素诱导的急性肾脏损伤具有保护作用。

Objective To investigate the protective effect of heparin combined with bupleuri injection on renal injury in endotoxin-induced rats.Methods The model of endotoxic renal injury was established by a single intraperitoneal of 7 mg/kg LPS in healthy SD rats.Eighteen endotoxic rats were randomly assigned into 3 groups(n=6 each):LPS group,heparin group,and heparin+Bupleurum group.The heparin group was injected with 120 U/kg heparin.Then,the heparin+Bupleurum group was treated by 120 U/kg heparin and 200 mg/kg bupleuri injection.In addition,eight healthy SD rats were selected as the control group which was given the same amount of saline.After drug administration for five hours,the blood sample and kidney tissue was taken.In the end,the parameters such as creatinine(CRE),fibrinogen(FIB),activated partial thromboplastin time(APTT),and renal pathology were compared between the groups.Results Compared with control group,longer APTT time,higher CRE levels,and lower FIB release were detected in LPS group(P<0.01):(53.80±19.37)s vs(19.70±3.25)s,(76.95±12.05)μmol/L vs(47.00±5.55)μmol/L,(53.17±12.95)mg/dL vs(440.89±44.64)mg/dL,respectively.At the same time,renal biopsy showed atrophic glomeruli and vascular engorgement in LPS group.Compared with LPS group,heparin group had significantly reduced APTT time and increased FIB release:(32.77±1.86)s vs(53.80±19.37)s,P<0.05;(399.01±56.66)mg/dL vs(53.17±12.95)mg/dL,P<0.01,but CRE level was similar between the two groups(P>0.05).Compared with LPS group,heparin combined with Bupleuri injection not only increased FIB release,but also reduced APTT time and CRE level:(368.50±41.32)mg/dL vs(53.17±12.95)mg/dL,P<0.01;(21.73±0.72)s vs(53.80±19.37)s,P<0.05;(52.53±13.14)μmol/L vs(76.95±12.05)μmol/L,P<0.01.While,the pathological change of kidney was alleviated in heparin+Bupleurum group.Conclusion Heparin anticoagulant therapy is not sufficient to reverse the renal damage caused by endotoxin.Heparin combined with Bupleurum has protective effect on endotoxin-induced acute kidney injury.