Oxidized LDL On Rat Mesangial Cells Inflammatory Effect And Blood Circulation Intervention

Both clinical and experimental studies have demonstrated that dyslipidemia plays an important role in the occurrence and development of kidney disease, especially hyperlipidemia. And ox-LDL is an important risk factor. Lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) is an specific receptor of ox-LDL which is very important in atherosclerosis (AS) and vascular inflammatory response. Recent studies have also confirmed that ox-LDL can promote the expression of inflammatory cytokines in process of AS, and inflammatory cytokines such as TNF-α plays an important role in the occurrence and development of AS. This study was designed to explore the inflammation effects of ox-LDL on rat mesangial cells(RMC), to confirm that ox-LDL may promote TNF-a expression mediated by LOX-1, a specific receptor. To investigate its possible molecular mechanism and provide a theoretical basis for the role of lipid peroxidation resulting in inflammation. And explore the intervention of blood circulation method on the ox-LDL-induced inflammatory injury by the use of blood serum containing Xuefuzhuyu decoction.This paper includes a review part and an experimental study part.Literature ReviewThe first review writes from atherosclerotic renal artery stenosis lead to renal ischemic injury, and hypertension leads to vascular atherosclerotic renal damage, to renal damage caused by hyperlipidemia, summarized the researches related to atherosclerotic renal damage.The second review describes the receptors of ox-LDL, and the researches on the physiological and pathological effects of ox-LDL on endothelial cells, smooth muscle cells, mesangial cells and other tissue.Experimental StudyObjective: By observing the injury on RMC from ox-LDL, to clear the inflammatory effects induced by ox-LDL, and uses blood serum containing Xuefuzhuyu decoction to intervene the inflammatory effects, to investigate intervention mechanism of blood circulation method on ox-LDL-induced inflammatory injury.Methods:In vitro cultivation of RMC, using different concentrations of ox-LDL to intervention for different duration, using the MTT assay to test the proliferation. Use50μg/ml ox-LDL to stimulated RMC for24h according to the results of MTT, using blood serum respectively containing simvastatin, Xuefuzhuyu decoction to intervene for24h. Detect the mRNA and protein levels of TNF-a and LOX-1via RT-PCR and Western blot.Results:1. ox-LDL intervened RMC for24h within the concentration of1-30μg/ml could promote the proliferation of RMC, when the concentration was higher than30μg/ml the proliferation was inhibited. The higher the concentration was, the greater the inhibition was. Intervened for48h, the proliferation was promoted within1-20μg/ml, and then began to inhibited when the concentration was higher than20μg/ml. Intervened for72h and the inhibitory effect was shown in various concentrations and duration. As the concentration increases, the inhibitory effect increased;2. Intervened RMC wi th50μg/ml ox-LDL for24h, the mRNA and protein express ion of TNF-α and LOX-1in model group were significantly higher than blank group (P<0.05);3. Intervened RMC with50μg/ml ox-LDL for24h, then intervened with blood serum, the protein expression of TNF-α and LOX-1were alleviated. Compared to model group, the TNF-α protein expression were decreased in simvastatin and Xuefuzhuyu decoction group(P<0.05). Compared to model group, the LOX-1protein expression were decreased in simvastatin and low-dosage, high-dosage Xuefuzhuyu decoction group.4. Intervened RMC with50μg/ml ox-LDL for24h, then intervened with blood serum, the mRNA expression of TNF-α and LOX-1were alleviated. Compared to model group, the TNF-a mRNA expression were decreased in Xuefuzhuyu decoct ion group(P<0.01). Compared to model group, the LOX-1mRNA expression were decreased in mid-dosage, high-dosage Xuefuzhuyu decoction group(P<0.05).Conclusion: The effect of ox-LDL on RMC proliferation is concentration-duration dependent. ox-LDL could cause inflammatory injury. Blood serum containing Xuefuzhuyu decoction could protect RMC from the inflammatory injury caused by ox-LDL, and inhibit the expression of LOX-1.