Experimental Research On The Relationship Between High-fat Diet And The Changes Of Blood Pressure In Rats

Objective: To investigate the relationship between high-fat diet and the changes of blood pressure,as well as the possible mechanism.Methods: 8-week-old male SD rats were adaptively fed for 1 week.Then,all of the rats were randomly divided into control group(ND,provided normal-diet),high-fat diet group(HFD,provided high-fat diet)and gentamicin group(GS,provided high-fat diet),as well as the blood pressure levels of the rats were measured as baseline levels.The body mass of rats was measured weekly.And then,the blood pressure levels of rats were measured once a week from the fifth week.At the ninth week,the GS group rats were intragastrically administered with gentamicin sulfate,the ND group and the HFD group rats were given normal saline.At last,all of the experimental rats were killed at the end of the13 th week,the levels of plasma glucose,lipid,endotoxin level,inflammatory factor concentration and insulin concentration were measured,as well as HOMA insulin resistance index(HOMA-IR)was calculated.Colonic feces of the rats were collected and the fecal bacterial genes were sequenced,and the differences of intestinal flora among the 3 groups were compared.The data were analyzed by repeated measures analysis of variance or one-way ANOVA and LSD test.Results: 1 The changes of systolic pressure in rats,At the first week,there were no significant differences in the levels of systolic blood pressure among the ND group(95.87±3.49 mm Hg),the HFD group(93.28±4.12 mm Hg)and the GS group(92.30±6.26 mm Hg)(P>0.05).At the end of the 5th week,the levels of systolic blood pressure of the ND group(102.66±6.29 mm Hg),the HFD group(114.32±9.40 mm Hg)and the GS group(117.26±11.57 mm Hg),Comparison among the three groups,Comparison of ND group with GS group and HFD group(P<0.05),Comparison of ND group with HFD group(P>0.05).At the end of the 10 th week,the levels of systolic blood pressure of the ND group(99.82±7.23 mm Hg),the HFD group(139.03±14.83 mm Hg)and the GS group(118.97±18.74 mm Hg),Comparison among the three groups,Comparison of GS group with ND group and HFD group(P<0.05),Comparison of ND group with HFD group(P>0.05).At the end of the 13 th week,the levels of systolic blood pressure of the ND group(101.44±6.11 mm Hg),the HFD group(142.55±9.43 mm Hg)and the GS group(98.65±8.43 mm Hg),Comparison among the three groups,Comparison of HFD group with ND group and GS group(P<0.05),Comparison of ND group with GS group(P>0.05).2 The Changes of body mass in rats,At the first week,there were no significant differences in the levels of body mass among the ND group(197.54±16.94g),the HFD group(199.71±23.50g)and the GS group(203.69±17.96g)(P>0.05).At the end of the 13 th week the body weight of ND group(410.09±47.35g),HFD group(409.08±47.25g)as well as the GS group(404.8±42.58g)were not statistically significant(P>0.05).3 The concentration of endotoxin and inflammatory factors in rats,At the end of the experiment,the concentration of plasma endotoxin of the ND group(0.006±0.001EU/ml),the HFD group(0.012±0.002EU/ml),and the GS group (0.009±0.002EU/ml),Comparison among the three groups,Comparison of GS group with ND group and HFD group(P<0.05),Comparison of ND group with HFD group(P<0.05).The concentration of IL-1 β of the ND group(90.90±26.67ng/ml),the HFD group(265.63±71.53ng/ml)and the GS group(106.6±34.84ng/ml),Comparison among the three groups,Comparison of HFD group with ND group and GS group(P<0.05),But comparison of GS group with ND group(P<0.05).The concentration of IL-6 of the ND group(137.5±58.37ng/ml),the HFD group(290±61.48ng/ml),and the GS group(195.5±36.92ng/ml),Comparison among the three groups,Comparison of HFD group with ND group and GS group(P<0.05),But comparison of GS group with ND group(P>0.05).The concentrations of TNF-α of the ND group(45.45±22.29ng/ml),the HFD group(103.63±47.22ng/ml),and the GS group(39.75±21.95ng/ml),Comparison among the three groups,Comparison of HFD group with ND group and GS group(P<0.05),But comparison of GS group with ND group(P>0.05).4 The changes of blood lipids,and insulin resistance in rats,The plasma total cholesterol(TC)levels of rats of the ND group(0.88±0.09mmol/L),the HFD group(1.24±0.19mmol/L)and the GS group(1.27±0.30mmol/L),Comparison among the three groups,Comparison of ND group with HFD group and GS group(P<0.05),But comparison of GS group with HFD group(P>0.05).The insulin resistances of the ND group(3.50±0.73),the HFD group(3.74±1.61)and the GS group(1.77±0.33),Comparison among the three groups,Comparison of GS group with HFD group and ND group(P<0.05),There was no statistical difference of insulin resistances between the ND group and the HFD group(P>0.05).5 The changes of intestinal microflora in experimental rats(1)Diversity index(Shannon index),The Shannon index of the ND group(4.85±0.27),the HFD group(4.62±0.28)and the GS group(4.22±0.29),Comparison among the three groups,Comparison of GS group with ND group(P<0.001),Comparison of GS group with HFD group(P<0.05),There was no significant difference of Shannon index between the ND group and the HFD group(P>0.05).(2)Richness index(ACE 、 Chao index),The ACE index of the ND group(725.10±72.07),the HFD group(713.31±54.20)and the GS group(478.05±90.19),Comparison among the three groups,Comparison of GS group with ND group and HFD group(P<0.001),There was no significant difference of ACE index between the ND group and the HFD group(P>0.05).The Chao index of the ND group(731.81±67.72),the HFD group(722.14±55.38)and the GS group(485.19±90.54),Comparison among the three groups,Comparison of GS group with ND group and HFD group(P<0.001),There was no significant difference of Chao index between the ND group and the HFD group(P>0.05).(3)The intestinal flora richness(phylum,class,order,family and genus level)(1)The phylum level of intestinal microflora in rats,There were no significant difference of the Firmicutes among the ND group(47.77±0.069)and the HFD group(39.6±0.14)as well as the GS group(49.32±0.19)(P>0.05).There were no significant difference of the Bacteroidetes among the ND group(42.94±0.09)and the HFD group(53.94±0.16)as well as the GS group (39.19±0.17)(P>0.05).There were no significant difference of the Proteobacteria among the ND group(6.04±0.04)and the HFD group(3.85±0.03)as well as the GS group(9.74±0.02)(P>0.05).The richness of Spirochaetae of the ND group(1.36±0.01),the HFD group(0.72±0.009)and the GS group(0.051±0.0007),Comparison among the three groups,Comparison of GS group with ND group(P<0.01),Comparison of GS group with HFD group(P<0.05),Comparison of ND group with HFD group(P>0.05).The richness of Saccharibacteria of the ND group(0.73±0.007),the HFD group(0.69±0.004)and the GS group(0.23±0.002),Comparison among the three groups,Comparison of GS group with HFD group and ND group(P<0.05),Comparison of ND group with HFD group(P>0.05).(2)The Class level of intestinal microflora in rats,The richness of Deltraproteobacteria of the ND group(2.86±0.017),the HFD group(1.46±1.35),and the GS group(0.67±0.006),Comparison among the three groups,Comparison of GS group with ND group(P<0.01),Comparison of GS group with HFD group(P>0.05),Comparison of ND group with HFD group(P>0.05).The richness of Spirochaetes of the ND group(1.36±0.012),the HFD group(0.79±0.009),and the GS group(0.051±0.0007),Comparison among the three groups,Comparison of GS group with ND group(P<0.01),Comparison of GS group with HFD group(P<0.05),Comparison of ND group with HFD group(P>0.05).The richness of Epsilonproteobacteria of the ND group(0.36±0.003),the HFD group(0.318±0.002)and the GS group(0.066±0.00007),Comparison among the three groups,Comparison of GS group with ND group and HFD group(P<0.01),Comparison of ND group with HFD group(P>0.05).The richness of Saccharibacteria of the ND group(0.73±0.007),the HFD group(0.758±0.004)and the GS group(0.230±0.002),Comparison among the three groups,Comparison of GS group with HFD group(P<0.05),Comparison of ND group with GS group and HFD group(P>0.05).The richness of Deferribacteres of the ND group(0.051±0.0005),the HFD group(0.032±0.0007)and the GS group(0.002±0.00006),Comparison among the three groups,Comparison of GS group with ND group(P<0.05),Comparison of HFD group with GS group and ND group(P>0.05).(3)The Order level of intestinal microflora in rats,The richness of O-Spirochaetates of the ND group(1.36±0.012),the HFD group(0.318±0.002)and the GS group(0.051±0.0007),Comparison among the three groups,Comparison of GS group with ND group(P<0.01),Comparison of GS group with HFD group(P<0.05),Comparison of ND group with HFD group(P>0.05).The richness of Campylobacterates of the ND group(0.307±0.000001),the HFD group(0.30±0.002)and the GS group(0.069±0.00007),Comparison among the three groups,Comparison of GS group with ND group(P<0.01),Comparison of HFD group with GS group and ND group(P>0.05).The richness of Aeromonadates of the ND group(1.62±0.02),the HFD group(0.511±0.005)and the GS group(0.028±0.0007),Comparison among the three groups,Comparison of GS group with ND group(P<0.01),Comparison of HFD group with ND group and GS group(P>0.05).The richness of Saccharibacte of the ND group(0.73±0.007),the HFD group (0.758±0.004)and the GS group(0.230±0.002),Comparison among the three groups,Comparison of GS group with ND group and HFD group(P<0.05),Comparison of ND group with HFD group(P>0.05).The richness of Desulfovibrionales of the ND group(0.84±0.017),the HFD group(1.465±0.013)and the GS group(0.664±0.006),Comparison among the three groups,Comparison of GS group with HFD group(P<0.01),Comparison of ND group with HFD group and GS group(P>0.05).(4)The Family level of intestinal microflora in rats,The richness of Rikenellaceae of the ND group(2.939±0.015),the HFD group(3.594±0.023)and the GS group(0.840±0.004),Comparison among the three groups,Comparison of GS group with HFD group and ND group(P<0.01),Comparison of ND group with HFD group(P>0.05).The richness of f-spirochaetaceae of the ND group(1.356±0.012),the HFD group(0.790±0.009)and the GS group(0.051±0.013),Comparison among the three groups,Comparison of GS group with ND group(P<0.01),Comparison of HFD group with ND group and GS group(P>0.05).The richness of f-unclassified-oBacteroidates of the ND group(0.906±0.006),the HFD group(0.869±0.01)and the GS group(0.192±0.019),Comparison among the three groups,Comparison of GS group with ND group(P<0.01),Comparison of GS group with HFD group(P<0.05),Comparison of ND group with HFD group(P>0.05).The richness of f-Vellionellaceae of the ND group(4.641±0.05),the HFD group(2.1±0.014)and the GS group(0.161±0.002),Comparison among the three groups,Comparison of GS group with ND group and HFD group(P<0.001), Comparison of ND group with HFD group(P>0.05).The richness of f-Desulfovibrionace of the ND group(1.691±0.015),the HFD group(2.835±0.017)and the GS group(0.664±0.006),Comparison among the three groups,Comparison of HFD group with ND group and GS group(P<0.05),Comparison of ND group with GS group(P>0.05).(5)The genus level of intestinal microflora in rats,The richness of g-Alloprevotella of the ND group(4.192±0.019),the HFD group(6.415±0.045)and the GS group(2.015±0.018),Comparison among the three groups,Comparison of GS group with HFD group(P<0.01),Comparison of GS group with ND group(P<0.05),Comparison of ND group with HFD group(P>0.05).The richness of g-Quinella of the ND group(4.156±0.054),the HFD group(1.813±0.012)and the GS group(0.085±0.002),Comparison among the three groups,Comparison of GS group with ND group(P<0.05),Comparison of HFD group with ND group and GS group(P>0.05).The richness of g-prevotellaceae-UCG-001 of the ND group(2.115±0.010),the HFD group(2.087±0.018)and the GS group(0.921±0.008),Comparison among the three groups,Comparison of GS group with ND group(P<0.05),Comparison of HFD group with ND group and GS group(P>0.05).The richness of g-Rikenellaceae-RC9-gut-group of the ND group(2.468±0.014),the HFD group(2.639±0.018)and the GS group(0.289±0.002),(P<0.05),Comparison of GS group with ND group(P<0.01),Comparison of GS group with HFD group(P<0.001),Comparison of ND group with HFD group(P>0.05).The richness of g-unclassified-Lachnospiraceae of the ND group(3.83±0.019),the HFD group(2.418±0.012)and the GS group(5.221±0.024),Comparison among the three groups,Comparison of GS group with HFD group(P<0.05),Comparison of HFD group with ND group and GS group(P>0.05).Conclusion: 1.High-fat diet could increase the level of endotoxin,TNF-α,IL-6 and IL-1 β in rats.The concentration of these inflammatory mediators could be reduced by gentamicin intragastric intervention.2.High-fat diet could increase the richness of the f-Desulfovibrionaceae family,but gentamicin intragastric intervention could reduce it.Moreover,gentamicin sulfate can reduce the abundance and diversity of the vast majority of the intestinal flora.3.High-fat diet could lead to increased blood pressure in rats,and the elevated blood pressure could be relieved by gentamicin sulfate intragastric intervention.4.High-fat diet could increase the level of endotoxin in rats by increasing the richness of the f-Desulfovibrionaceae family.High endotoxemia caused the increase in the concentration of inflammatory factors,then led to the elevated of blood pressure.Gentamycin could reduce plasma endotoxin level in rats by reducing the f-Desulfovibrionaceae family richness so that control the concentration of inflammatory factors and insulin resistance,thereby relieving the elevated blood pressure.