Lactobacillus Acidophilus Regulates NO And Its Oxidative Mediator In Atherosclerosis

Objective: Atherosclerosis(AS)is one of the most common and serious diseases affecting human health in the cardiovascular system.It has been a very active field for its etiology,pathogenesis and prevention.As a key signaling molecule that regulates platelet aggregation and reduces oxidative inflammatory response,NO is an important protective factor for vascular endothelial cells.Its reduced content and reduced bioavailability can cause endothelial cell damage and lead to the progression of atherosclerosis.To research the mechanism of Lactobacillus acidophilus against atherosclerosis by investigating the effects of Lactobacillus acidophilus on nitric oxide(NO)and its oxidative mediators and channels.Methods: Twenty-four SPF male rats were randomly divided into normal diet group,High fat diet + inflammatory stimulation group(high fat group)and High fat diet + inflammatory stimulation + Lactobacillus acidophilus group(Lactobacillus acidophilus group),with 8 rats in each group.Then feeding in different ways in the same environment:The rats in the normal diet group were fed with normal diet,and the high fat group was fed with high-fat diet + intraperitoneal injection of vitamin D3 + immune injury + FeSO4 to establish an atherosclerosis model.The rats in the Lactobacillus acidophilus group were intragastrically administered with 0.5 mL of Lactobacillus acidophilus per day(1×109 CFU/mL)on the basis of the high-fat group,each of them were weighed at the 4th,8th and 12 th weekends.After 12 weeks of feeding,the serum was taken from abdominal aorta to detect the content of oxidized low density lipoprotein(oxLDL),NO,arginine,arginase,and peroxynitrite(ONOO-).The aorta was isolated to observe the morphological change by HE staining,The expression of eNOS and iNOS mRNA was detected by Real-time PCR,and the expression of NF-κB p65 subunit was detected by Western blot.Results:(1)There was no significant difference in body weight between the high-fat group and the Lactobacillus acidophilus group during the whole experiment(P>0.05),but it was significantly increased compared with the normal diet group(P < 0.01).(2)HE staining showed that the aorta formed a wide range of atherosclerotic lesions in the high-fat rats,and the aortic morphology in the Lactobacillus acidophilus group was significantly improved.Only endothelial cells proliferated,and no smooth muscle cell necrosis was observed in this group.(3)Compared with normal diet group,the expression of serum oxLDL,ONOO-,arginase,aortic iNOS mRNA and nuclear NF-κB p65 were increased in high-fat group(P<0.01),the serum arginine content and aortic eNOS mRNA expression levels were decreased(P<0.01).While Lactobacillus acidophilus can just reverse the above changes(P < 0.01).Conclusion:(1).Lactobacillus acidophilus can reduce the formation of atherosclerosis in rats with high fat diet;(2).Lactobacillus acidophilus can reduce the production of inflammatory markers such as oxLDL,ONOO-,and arginase in serum of rats with high-fat diet;(3).Lactobacillus acidophilus can increase NO production and increase NO bioavailability by increasing the expression of eNOS mRNA and reducing the expression of iNOS mRNA;(4).Lactobacillus acidophilus can inhibit the transfer of NF-κB p65 subunit from cytoplasm to nucleus,and reduce the expression of NF-κB signaling pathway to inhibit the progression of oxidative inflammation.