Effect of Lumbricus Peptides on TLR4/NF-<i>κ</i>B Signaling Pathway in Spontaneous Hypertensive Rat Kidney / 中国实验方剂学杂志

ABSTRACT

@# <b>Objective:</b>to observe the effect and mechanism of lumbricus peptides on early renal injury in spontaneous hypertensive rats (SHR) based on Toll-like receptors 4 (TLR4)/nuclear factor-<i>κ</i>B(NF-<i>κ</i>B) signaling pathway. <b>Method:</b>The 40 SHRs were randomly divided into model group (equal volume of distilled water by intragastric administration), lumbricus peptides low, middle and high dose groups (126, 252, 504 mg·kg^-1), and Benazepril group (0.9 mg·kg^-1), <i>n</i>=8 in each group. 8 male rats with normal blood pressure at the same age were set as the normal control group,with equal volume of distilled water. After treatment for 60 consecutive days, enzyme-linked immunosorbent assay (ELISA) was used to determine microalbumin (mAlb)and <i>N</i>-acetyl-<i>β</i>-<i>D</i>-glucosaminidase (NAG) content in 24 h urine as well as the level of serum angiotensinⅡ (AngⅡ). Ultrastructural changes of rat kidneys were observed by transmission electron microscope. Western blot was used to detect renal TLR4, NF-<i>κ</i>B p65 protein levels. Immunohistochemical method was used to detect renal tumor necrosis factor-<i>α</i> (TNF-<i>α</i>) and interleukin 10 (IL-10) expression. <b>Result:</b>As compared with the normal control group, the levels of urine mAlb, NAG and serum Ang Ⅱ were increased in the model group (<i>P</i><0.05); the expression of TLR4 and NF-<i>κ</i>B p65 protein was increased (<i>P</i><0.05); expression of TNF-<i>α</i> was increased (<i>P</i><0.05), while IL-10 expression was decreased (<i>P</i><0.05). Transmission electron microscopy of kidney tissues showed that most of the glomeruli of the model group had podocyte foot process fusion, mesangial cells and mesangial matrix hyperplasia. As compared with the model group, the levels of urine mAlb, NAG, and serum Ang Ⅱ were decreased in the rats in lumbricus peptides groups and benazepril group (<i>P</i><0.05); the expression of TLR4 and NF-<i>κ</i>B p65 protein was decreased (<i>P</i><0.05); the positive expression of TNF-<i>α</i> in kidney was decreased to different extent (<i>P</i><0.05), but the expression of IL-10 was increased (<i>P</i><0.05). Transmission electron microscopy of kidney tissues showed that the damage of kidneys in rats after administration of high-dose lumbricus peptides and benazepril was improved in varying degrees. <b>Conclusion:</b>lumbricus peptides can reduce early renal damage in SHRs, and its mechanism may be achieved by regulating the AngⅡ-TLR4/NF-<i>κ</i>B pathway.