Dopamine Pretreatment Protects Offspring Rats from LPS-Induced Hypertension and Kidney Damage by Inhibiting NLRP3 Activation in Kidney
This study was designed to explore the role of dopamine (DA) and NLRP3 in the mechanism of hypertension and renal impairment induced by prenatal exposure to lipopolysaccharide (LPS). Thirty pregnant rats were randomly divided into three groups, including control, LPS, and DA + LPS groups. Renal morphology changes were observed under microscope. The serum IL-1β and IL-18 concentration, mRNA, and protein expressions of NLRP3, ASC, and CASP1 in kidney of three-month old offspring rats were measured. Hematoxylin–eosin staining showed that the glomerular diameter decreased and cysts increased partly, glomerular balloons were adhered partly, there were moderate-to-severe hyperplasia dispersedly distributed in glomerular mesangial matrix in rats of LPS group. Serum IL-1β and IL-18 concentration in LPS group increased compared with control group and DA + LPS group. The average arterial pressure of offspring rats in LPS group increased significantly compared with control group and DA + LPS group. NLRP3 mRNA level in the LPS group increased significantly compared with the control group and the DA + LPS group in both male and female rats; NLRP3, ASC, and CASP1 protein expression in both renal cortex and renal medulla of LPS group increased significantly compared with control group and DA + LPS group in female rats. NLRP3 protein expression in LPS group increased significantly compared with control group and DA + LPS group in male rats. DA pretreatment exerts a protective effect on LPS-induced renal injury and hypertension in offspring rats, and the mechanism might be through inhibiting NLRP3 activation.
Keywordsprenatal stress lipopolysaccharide hypertension dopamine NLRP3 inflammation
nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3
apoptosis-associated speck-like protein containing a caspase recruitment domain
pathogen-associated molecular patterns
danger-associated molecular patterns
dopamine 1 receptor
blood urea nitrogen
enzyme-linked immunosorbent assay
hematoxylin and eosin
Toll-like receptor 4
acute kidney injury
acute tubular necrosis
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- 9.Li, X., Liu, S., Luo, J., Liu, A., Tang, S., Liu, S., Yu, M., and Zhang, Y., Pathog. Dis., 2015, vol. 73, no. 4, pii: ftu024. doi 10.1093/femspd/ftu024Google Scholar