枸杞蛋白酶解液对自发性高血压大鼠的降血压机制研究

Anti-hypertensive Mechanism of the Enzymatic Hydrolysate of Lycium barbarum Protein on Spontaneously Hypertensive Rats

目的:探讨枸杞蛋白酶解液对自发性高血压大鼠(SHR)肾素血管紧张素系统(RAS)的影响及其可能的降压机制。方法:分别灌胃SPF级Wistar大鼠近交系雄性SHR大鼠生理盐水、10 mg/kg卡托普利、枸杞蛋白酶解液低剂量组(40 mg/kg)、枸杞蛋白酶解液中剂量组(80 mg/kg)、枸杞蛋白酶解液高剂量组(100 mg/kg),Wistar-Kyoto(正常大鼠,WKY)作为正常对照组灌胃生理盐水,共9周。采用酶联免疫吸附法测定其血浆中血管紧张素Ⅱ(AngⅡ)的含量,采用实时荧光定量PCR(RT-qPCR)方法测量心脏和肾脏组织中的血管紧张素转换酶(ACE)、血管紧张素Ⅱ1型受体(AT1-R)、血管紧张素转换酶2(ACE2)和Mas受体(Mas-R) mRNA的表达水平。结果:与WKY组相比,SHR大鼠的进食量显著增加而体重均显著低于WKY组(p <0.05),其收缩压(SBP)与舒张压(DBP)均显著升高(p <0.05),血浆中AngⅡ含量明显升高,ACE、AT1-R mRNA表达上调,而ACE2、Mas-R mRNA表达下调;与生理盐水处理组SHR大鼠比较,卡托普利组体重显著降低(p <0.05);卡托普利组、低、中、高剂量组SHR大鼠的SBP均显著下降(p <0.05);其中枸杞蛋白酶解液低剂量组显著降低SHR大鼠血浆中AngⅡ含量(p <0.05),下调心脏及肾脏组织中ACE mRNA表达水平(p <0.05),上调ACE2 mRNA表达水平(p <0.05)。结论:枸杞蛋白酶解液可以有效降低SHR大鼠的血压,其作用机制可能是通过抑制ACE活性,下调ACE、AngⅡ和AT1-R mRNA表达水平,上调ACE2和Mas-R mRNA表达水平起到降压作用。

Objective: The paper was to explore the effects of enzymatic hydrolysate of Lycium barbarum protein on the reninangiotensin system( RAS) in spontaneously hypertensive rat( SHR) and its possible antihypertensive mechanism. Methods: SPF wistar rat inbred line male SHR were respectively given saline solution,10 mg/kg of captopril,low-dose group of enzymatic hydrolysate of Lycium barbarum protein( 40 mg/kg),middle-dose group( 80 mg/kg),and high-dose group( 100 mg/kg) by gavage.Wistar-kyoto( normal rats,WKY) served as normal control group were given saline solution by gavage for 9 consecutive weeks.The contents of plasma angiotensin Ⅱ( Ang Ⅱ) was detected by enzyme-linked immunosorbent assay,the mRNA expression levels of angiotensin-converting enzyme( ACE),AngⅡ type 1 receptor( AT1-R),angiotensin-converting enzyme 2( ACE2) and mas receptor( Mas-R) in heart and kidney tissues were analyzed by RT-qPCR( real-time fluorescent quantitative polymerase chain reaction) method.Results: Compared with WKY,the food intake of SHR increased significantly and the body weight was significantly lower than WKY group( p < 0.05),the systolic blood pressure( SBP) and diastolic blood pressure( DBP) of SHR were significantly increased( p < 0.05). The contents of Ang Ⅱ in plasma were obviously increased. The expression of ACE and AT1-R mRNA were up-regulated,while ACE2 and Mas-R mRNA were down-regulated. Compared with saline-treated SHR,the weight of captopril-treated group decreased significantly( p < 0.05),the SBP of captopril-treated group,low-dose,middle-dose,and high-dose group were significantly decreased( p < 0.05).Among them,the low-dose group of enzymatic hydrolysate of Lycium barbarum protein could significantly decrease the contents of AngⅡ in plasma of SHR( p <0.05),down-regulation of the expression of ACE mRNA( p < 0.05) in heart and kidney tissues,and up-regulation of the expression of ACE2 mRNA( p < 0.05). Conclusion: The enzymatic hydrolysate of Lycium barbarum protein could effectively decrease the blood pressure of SHR. The mechanism might be through inhibiting the activity of ACE,down-regulation of the expression of ACE,AngⅡ and AT1-R mRNA and up-regulation of expression of ACE2 and mas-R mRNA to achieve antihypertensive effect.