Radix Astragali Normalizes The Gene Expression Of Angiotensin-Converting Enzyme 2 On The Kidney In Rat Model Of Metabolic Syndrome

Objective Angiotensin-converting enzyme2(ACE2) is an important peptide in renin-angiotensin system(RAS) and becoming a new target for hypertension and diabetes. At the same time, RAS have a close relationship with metabolic syndrome(MS). The present study was designed to investigate the renal function, morphology and the gene expression of ACE2 and angiotensin-converting enzyme(ACE) on kidney of rat model with metabolic syndrome, and to evaluate the effect of Radix Astragali, a kind nature herb, on them.Methods Sixty adult male Wistar rats were grouped randomly as follows: normal control group (n=10); fructose-induced MS group (n=10); MS+valsartan 20mg /(kg·d) group (valsartan group, n=10); MS+Radix Astragali 1.5g /(kg·d)group (low dose group, n=10);MS+Radix Astragali 3.0g/(kg·d)group (middle dose group,n=10) and MS+Radix Astragali 6.0g /(kg·d)group (high dose group,n=10). After 6 weeks of treatment, the metabolism indexes included SBP, visceral fat/weight ratio, TG,FFA and ISI were achieved to confirm the models establishing and to evaluate the effect of Radix Astragal on them, all rats were sacrificed and kidneys were harvested for following studies: Serum creatinine(Scr) and blood urea nitrogen(BUN) in all groups were evaluated with an automatic chemisty analyzer. HE staining was performed to observe the renal morphological changes. Real time PCR and immunohistochemistry were used to judge the changes of ACE and ACE2 in kidney separately. Moreover, AngiotensinⅡ(AngⅡ) of kidney was measured with radioimmunoassay.Results①There were significant deviation of SBP and others metabolic indexes between MS group and normal control group[SBP(144.5±3.3mmHg vs 109.3±5.0mmHg, P=0.000), visceral fat/weight ratio (0.044±0.001 vs 0.037±0.002, P=0.000), TG (1.74±0.10mmol/L vs 1.18±0.19mmol/L, P=0.000), FFA(457.6±49.1μmol/L vs 345.0±65.9μmol/L,P=0.000) increased obviously,ISI was decreased(-5.26±0.16 vs - 4.48±0.06, P=0.000)]. Compared with the normal control group, AngⅡof kidney tissue in MS group was increased statistically(20.53±1.87pg/mg vs 13.38±1.38pg/mg,P=0.000). The expression of ACE mRNA in MS group was up regulated of 76% than that in normal control group, while ACE2mRNA was down regulated of 58% (1.76±0.12 vs 1.00±0.13, P=0.000; 0.42±0.07 vs 1.00±0.07, P=0.000).②Both valsartan and Radix Astragali improved the metabolic indexes[SBP(122.1±4.6mmHg,136.0±3.90mmHg, 127.5±3.6mmHg, 116.3±4.4mmHg) vs (144.5±3.3mmHg), P=0.000, P=0.000,P=0.000,P=0.000. Visceral fat/weight ratio(0.041±0.001, 0.043±0.001, 0.040±0.001, 0.038±0.002) vs (0.044±0.001), P=0.000, P=0.441, P=0.000, P=0.000. TG(1.52±0.11mmol/L, 1.63±0.13mmol/L, 1.47±0.09mmol/L, 1.27±1.00mmol/L) vs (1.74±0.10mmol/L),P=0.004, P=0.762, P=0.000, P=0.000. FFA(406.6±41.9μmol/L, 429.1±29.0μmol/L, 400.1±30.6μmol/L, 365.1±27.5μmol/L) vs (457.6±49.1μmol/L), P=0.043, P=1.000, P=0.013, P=0.000. ISI(-4.97±0.13,-5.13±0.10,-4.81±0.11,-4.64±0.12) vs (-5.26±0.16),P=0.000, P=0.222, P=0.000, P=0.000]. The level of AngⅡof kidney tissue was found to be higher in valsartan group compared with that in MS group(27.47±2.50pg/mg vs 20.53±1.87pg/mg,P=0.000), while decreased in Radix Astragali group (Radix Astragali low dose group: 17.94±1.63pg/mg, Radix Astragal middle dose group:15.90±1.75pg/mg, Radix Astragal high dose group:13.96±1.36pg/mg) vs (MS group: 20.53±1.87pg/mg), P=0.031,P=0.000,P=0.000.③Both Radix Astragali and Valsartan improved the level of ACE2mRNA gene(Valsartan group: 0.70±0.08, Radix Astragal low dose group: 0.57±0.09, Radix Astragal middle dose group: 0.67±0.08, Radix Astragal high dose group: 0.84±0.10 vs MS group: 0.42±0.07, P=0.000,P=0.002,P=0.000 and P=0.000 respectively) and protein content of ACE2 (Valsartan group: 0.29±0.03, Radix Astragal low dose group: 0.22±0.03, Radix Astragal middle dose group: 0.27±0.02, Radix Astragal high dose group: 0.38±0.04 vs MS group:0.18±0.02, P=0.000, P=0.020,P=0.000 and P=0.000 respectively). These two medicines also could lower the level of expression of ACEmRNA (Valsartan group:1.36±0.1,Radix Astraga low dose group:1.53±0.13, Radix Astraga middle dose group: 1.33±0.1, Radix Astraga high dose group: 1.17±0.09 vs MS group: 1.76±0.12,P=0.000, P=0.001, P=0.000 and P=0.000 respectively).④There was good linear regression correlation among AngⅡand metabolic indices as a function of ACE2mRNA. But multiple regressions found that when these indicators existed at the same time, due to the interaction among them, only SBP and the ISI possessed linear regression relations with the ACE2.⑤Finally, there were no difference of Scr and BUN within these groups but renal morphological study showed the improvement in Valsartanand Radix Astragali groups compared with MS control group.Conclusions Intrarenal RAS disorder was confirmed in MS, which included morphological change, the balance between ACE and ACE2 and the level of AngⅡin renal tissue. Radix Astragali as a herb medicine has the similar capability with Valsatan torecuperate this balance, improve the metabolic indexes and renal morphological changes and there for to protect the kidney function of MS.