Abstract:

Objective　To observe the effects of extracts of laggera herb on renal function and nuclear transcription factor κB (NF-κB) signaling pathway in myocardial infarction rats. Methods　Fifty SPF-grade SD rats were selected, half male and half female, aged 4-6 weeks, weighted 200-300 g, a sham surgery group, a myocardial infarction group, and three experimental groups receiving different doses of the extracts of laggera herb, 10 rats in each group. The doses were 6.8 g/kg, 13.6 g/kg, and 27.2 g/kg of the extracts diluted in distilled water, administered via gavage for 14 d. The cardiac function [left ventricular end-diastolic pressure (LVEDP), mean arterial pressure (MAP), left ventricular systolic pressure and (LVSP)], renal function [creatinine (Cr), urea nitrogen (BUN), and 24 h urine protein], inflammatory factors [interleukin (IL) -1β, IL-6, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor α (TNF-α)], pathological changes of myocardial and renal tissues, renal histopathological protein levels (NF-κB, p65, p-p65, and IκBβ), and renal mRNA levels (NF-κB and IκBβ) were compared between among all groups after the last gavage. Independent sample t test and one-way analysis of variance were used for statistical analysis. Results　After the last gavage, the LVEDP in the model group was higher than that in the sham surgery group, but the MAP and LVSP were lower than those in the sham surgery group (all P<0.05); the LVEDP in the low, medium, and high dose groups were lower than that in the model group, but the MAP was higher than that in the model group (all P<0.05); the LVEDP in the high dose group was lower than those in the low and medium dose groups [(8.17±0.38) mmHg (1 mmHg=0.133 kPa) vs. (11.59±0.22) mmHg and (9.86±0.41) mmHg], and the MAP and LVSP were higher than those in the low and medium dose groups [(116.33±4.24) mmHg vs. (101.26±4.02) mmHg and (105.86±3.63) mmHg, (140.67±5.65) mmHg vs. (113.59±7.88) mmHg and (129.86±6.02) mmHg] (all P<0.05). The levels of serum Cr, BUN, and 24 h urinary protein in the model group were higher than those in the sham surgery group (all P<0.05); serum Cr and 24 h urinary protein levels in the low, medium, and high dose groups were lower than those in the model group (all P<0.05); serum Cr, BUN, and 24 h urinary protein levels in the high dose group were lower than those in the low and medium dose groups [(14.33±5.33) μmol/L vs. (39.26±6.42) μmol/L and (27.52±5.61) μmol/L, (8.14±0.24) mmol/L vs. (11.59±2.00) mmol/L and (9.86±0.22) mmol/L, (7.00±0.76) mg vs. (11.59±1.78) mg and (9.52±1.02) mg] (all P<0.05). Serum levels of IL-1β, IL-6, MCP-1, and TNF-α in the model group were higher than those in the sham surgery group (all P<0.05); serum levels of IL-6 and MCP-1 in the low, medium, and high dose groups were lower than those in the model group (all P<0.05); serum levels of IL-1β, IL-6, MCP-1, and TNF-α in the high dose group were lower than those in the low dose group [(23.64±0.07) ng/L vs. (28.59±4.87) ng/L, (16.57±0.37) ng/L vs. (21.86±1.89) ng/L, (225.64±20.35) ng/L vs. (321.56±17.36) ng/L, (14.46±0.51) ng/L vs. (21.30±2.78) ng/L] (all P<0.05). The protein levels of NF-κB and p-p65/p65 in the kidney tissue of the model group were higher than those in the sham surgery group, and the protein level of IκBβ was lower than that in the sham surgery group (all P<0.05); the protein levels of NF-κB and p-p65/p65 in the low, medium, and high dose groups were lower than those in the model group, and the protein levels of IκBβ were higher than that in the model group (all P<0.05); the protein levels of NF-κB and p-p65/p65 in the high dose group were lower than those in the low and medium dose groups (0.18±0.02 vs. 0.34±0.02 and 0.25±0.01, 0.34±0.02 vs. 0.67±0.01 and 0.46±0.02), and the protein level of IκBβ was higher than those in the low and medium dose groups (0.42±0.02 vs. 0.26±0.01 and 0.33±0.02) (all P<0.05). The NF-κB mRNA level in the model group was higher than that in the sham surgery group, and the IκBβ mRNA level was lower than that in the sham surgery group (both P<0.05); the NF-κB mRNA levels in the medium and high dose groups were lower than that in the model group, and the IκBβ mRNA levels were higher than that in the model group (all P<0.05); the NF-κB mRNA level in the high-dose group was lower than that in the low-dose group (1.26±0.16 vs. 1.90±0.25), and the IκBβ mRNA level was higher than that in the low-dose group (0.94±0.10 vs. 0.69±0.09) (both P<0.05). Conclusions　The extract of laggera herb can effectively improve the cardiac and renal function and relieve the pathological injury of myocardium and renal tissues in rats with myocardial infarction. The molecular mechanism may be related to inhibiting the activation of NF-κB signaling pathway.

Key words:

Extract of laggera herb, Myocardial infarction, NF-κB signaling pathway, Kidney function, Cardiac function

摘要：

目的　观察六棱菊提取物对心肌梗死大鼠肾功能及核转录因子κB（NF-κB）信号通路的影响。方法　选取SPF级SD大鼠50只，雄雌各半，鼠龄4～6周，体重200～300 g。假手术组、心肌梗死组（模型组）、低剂量六棱菊提取物组（低剂量组）、中剂量六棱菊提取物组（中剂量组）和高剂量六棱菊提取物组（高剂量组），每组10只大鼠。低、中、高剂量组采用无菌蒸馏水稀释的六棱菊提取物（6.8 g/kg、13.6 g/kg、27.2 g/kg）灌胃，假手术组和模型组采用等体积生理盐水灌胃，5组均持续灌胃14 d。比较最后1次灌胃完成后各组心脏功能［左心室舒张末期压力（LVEDP）、平均动脉压（MAP）、左心室收缩压（LVSP）］、肾功能［肌酐（Cr）、尿素氮（BUN）、24 h尿蛋白］、炎症因子［白细胞介素（IL）-1β、IL-6、单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子α（TNF-α）］、心肌和肾脏组织病理变化、肾脏组织蛋白水平（NF-κB、p65、p-p65、IκBβ）、肾脏组织mRNA水平（NF-κB、IκBβ）。采用独立样本t检验和单因素方差分析进行统计学分析。结果　最后1次灌胃完成后，模型组LVEDP高于假手术组，MAP和LVSP均低于假手术组（均P<0.05）；低、中、高剂量组LVEDP均低于模型组，MAP均高于模型组（均P<0.05）；高剂量组LVEDP低于低、中剂量组［（8.17±0.38）mmHg（1 mmHg=0.133 kPa）比（11.59±0.22）mmHg、（9.86±0.41）mmHg］，MAP和LVSP均高于低、中剂量组［（116.33±4.24）mmHg比（101.26±4.02）mmHg、（105.86±3.63）mmHg，（140.67±5.65）mmHg比（113.59±7.88）mmHg、（129.86±6.02）mmHg］（均P<0.05）；模型组血清Cr、BUN和24 h尿蛋白水平均高于假手术组（均P<0.05）；低、中、高剂量组血清Cr和24 h尿蛋白水平均低于模型组（均P<0.05）；高剂量组血清Cr、BUN和24 h尿蛋白水平均低于低、中剂量组［（14.33±5.33）μmol/L比（39.26±6.42）μmol/L、（27.52±5.61）μmol/L，（8.14±0.24）mmol/L比（11.59±2.00）mmol/L、（9.86±0.22）mmol/L，（7.00±0.76）mg比（11.59±1.78）mg、（9.52±1.02）mg］（均P<0.05）；模型组血清IL-1β、IL-6、MCP-1和TNF-α水平均高于假手术组（均P<0.05）；低、中、高剂量组血清IL-6和MCP-1水平均低于模型组（均P<0.05）；高剂量组血清IL-1β、IL-6、MCP-1和TNF-α水平均低于低剂量组［（23.64±0.07）ng/L比（28.59±4.87）ng/L，（16.57±0.37）ng/L比（21.86±1.89）ng/L，（225.64±20.35）ng/L比（321.56±17.36）ng/L，（14.46±0.51）ng/L比（21.30±2.78）ng/L］（均P<0.05）；模型组肾脏组织NF-κB和p-p65/p65蛋白水平均高于假手术组，IκBβ蛋白水平低于假手术组（均P<0.05）；低、中、高剂量组NF-κB和p-p65/p65蛋白水平均低于模型组，IκBβ蛋白水平均高于模型组（均P<0.05）；高剂量组NF-κB和p-p65/p65蛋白水平均低于低、中剂量组（0.18±0.02比0.34±0.02、0.25±0.01，0.34±0.02比0.67±0.01、0.46±0.02），IκBβ蛋白水平高于低、中剂量组（0.42±0.02比0.26±0.01、0.33±0.02）（均P<0.05）；模型组肾脏组织NF-κB mRNA水平高于假手术组，IκBβ mRNA水平低于假手术组（均P<0.05）；中、高剂量组NF-κB mRNA水平均低于模型组，IκBβ mRNA水平均高于模型组（均P<0.05）；高剂量组NF-κB mRNA水平低于低剂量组（1.26±0.16比1.90±0.25），IκBβ mRNA水平高于低剂量组（0.94±0.10比0.69±0.09）（均P<0.05）。结论　六棱菊提取物可有效改善心肌梗死大鼠心脏和肾功能，减轻心肌及肾脏组织病理损伤，分子机制可能与抑制NF-κB信号通路激活相关。

关键词:

六棱菊提取物, 心肌梗死, NF-κB信号通路, 肾功能, 心脏功能