人参二醇组皂苷联合依拉达奉对内毒素休克大鼠心肺损伤的保护作用

Protective effect of panaxadiol saponins combined with edaravone on cardiopulmonary injury rats with endotoxic shock

目的研究人参二醇组皂苷联合依拉达奉对内毒素休克大鼠心肺损伤保护作用。方法将40只Wistar大鼠随机分为假手术组、模型组、阳性对照组和实验组,每组10只。模型组、阳性对照组和实验组均经股静脉注射大肠杆菌脂多糖(LPS)建立内毒素休克大鼠模型,假手术组注射生理盐水1 mL,建模后,假手术组和模型组经股静脉注射生理盐水0.5 mL,阳性对照组经股静脉注射地塞米松3 mg·kg^(-1),实验组经股静脉注射人参二醇组皂苷45 mg·kg^(-1)+依拉达奉3 mg·kg^(-1)。给药后4 h后,检测各组大鼠血清酶及肺组织中氧化应激指标水平;用免疫组化法检测各组大鼠肺组织中基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶组织抑制因子-2(TIMP-2)蛋白表达情况;用苏木精-伊红染色法(HE)观察各组大鼠肺组织形态学变化。结果给药后,模型组血清肌酸激酶(CK)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)分别为(1025.12±368.45),(526.48±201.52),(634.58±267.41)U·L^(-1),阳性对照组分别为(562.34±211.26),(286.45±232.15),(359.48±105.36)U·L^(-1),实验组分别为(389.45±268.47),(252.36±124.51),(298.46±169.74)U·L^(-1)。阳性对照组和实验组上述指标与模型组相比,差异均有统计学意义(均P<0.01)。模型组大鼠肺组织中MMP-2和TIMP-2分别为0.24±0.06,0.15±0.04,假手术组分别为0.09±0.02,0.14±0.02,阳性对照组分别为0.16±0.04,0.15±0.04,实验组分别为0.18±0.05,0.16±0.03。模型组与假手术组比较,差异均有统计学意义(均P<0.01);实验组和阳性对照组与模型组比较,差异均有统计学意义(均P<0.01)。结论人参二醇组皂苷联合依拉达奉可减轻内毒素休克大鼠肺组织炎性程度,下调肺组织MMP-2表达,同时对心肌也具有一定的保护作用。

Objective To investigate the protective effects of panaxadiol saponins combined with edaravone on cardiopulmonary injury rats with endotoxic shock. Methods Forty Wistar rats were randomly divided into sham operation group, model group, positive control group and test group, each group 10 rats. The model group, positive control group and test group were injected with Escherichia coli lipopolysaccharide （LPS） to establish the endotoxic shock rat model, sham operation group was in- jected with normal saline 1 mL. After modeling, sham operation group and model group were injected with normal saline 0.5 mL through femoral vein, positive control group was injected with dexamethasone 3 mg·kg-1 through femoral vein, test group was injected with panaxadiol saponins 45 mg·kg-1＋ edaravone 3 mg·kg-1 through femoral vein. The levels of serum enzyme and oxidative stress in lung tissues were measured 4 h after drug intervention, the expression of matrix metalloproteinase - 2 （ MMP - 2 ） and tissue inhibitor of metalloproteinase - 2 （ TIMP - 2 ） in lung tissue of each group were detected by immunohistochemistry, hematoxylin - eosin （ HE ） staining was used to observe the morphological changes of lung tissue in rats. Results After 4 h intervention, the levels of serum ereatine kinase （CK）, aspartate aminotransferase （AST）, lactate dehydrogenase （LDH） in model group were （1025.12±368.45）, （526.48±201.52）, （634.58±267.41） U·L-1, and were （562.34 ±211.26）, （286.45±232.15）, （359.48±105.36）U·L-1 in positive group, which were （389.45±268.47）, （252. 36 ± 124. 51 ）, （298.46 ± 169. 74）U·L-1 in test group. The levels of above index in positive group and test group had significant difference with those in model group（ P 〈0. 01 ）. The levels of MMP- 2 and TIMP- 2 in model group were 0. 24± 0. 06 and 0. 15±0. 04 in lung tissue, and were 0. 09 ± 0. 02 and 0. 14± 0. 02 in sham operation group and 0. 16 ±0. 04 and 0. 15 ±0. 04 in positive control group, and were 0. 18±0. 05,0. 16±0. 03 in experimental group. The difference between model group and sham operation group was statistically significant （all P 〈0. 01 ）. The difference between experimental group and positive control group and model group was statistically significant （all P 〈 0. 01 ）. Conclusion Panaxadiol saponins combined with edaravone can reduce the oxidative stress and inflammatory degree of lung injury in endotoxin shock rats, down - regulate the expression of MMP - 2 in lung tissue, and also protect the myoeardium.