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

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