Expression of LRG-1 in mice with hypertensive renal damage and its significance / 中南大学学报(医学版)

OBJECTIVES@#Long-term elevated blood pressure may lead to kidney damage, yet the pathogenesis of hypertensive kidney damage is still unclear. This study aims to explore the role and significance of leucine-rich alpha-2-glycoprotein-1 (LRG-1) in hypertensive renal damage through detecting the levels of LRG-1 in the serum and kidney of mice with hypertensive renal damage and its relationship with related indexes.@*METHODS@#C57BL/6 mice were used in this study and randomly divided into a control group, an angiotensin II (Ang II) group, and an Ang II+irbesartan group. The control group was gavaged with physiological saline. The Ang II group was pumped subcutaneously at a rate of 1.5 mg/(kg·d) for 28 days to establish the hypertensive renal damage model in mice, and then gavaged with equivalent physiological saline. The Ang II+irbesartan group used the same method to establish the hypertensive renal damage model, and then was gavaged with irbesartan. Immunohistochemistry and Western blotting were used to detect the expression of LRG-1 and fibrosis-related indicators (collagen I and fibronectin) in renal tissues. ELISA was used to evaluate the level of serum LRG-1 and inflammatory cytokines in mice. The urinary protein-creatinine ratio and renal function were determined, and correlation analysis was conducted.@*RESULTS@#Compared with the control group, the levels of serum LRG-1, the expression of LRG-1 protein, collagen I, and fibronectin in kidney in the Ang II group were increased (all P<0.01). After treating with irbesartan, renal damage of hypertensive mice was alleviated, while the levels of LRG-1 in serum and kidney were decreased, and the expression of collagen I and fibronectin was down-regulated (all P<0.01). Correlation analysis showed that the level of serum LRG-1 was positively correlated with urinary protein-creatinine ratio, blood urea nitrogen, and blood creatinine level in hypertensive kidney damage mice. Serum level of LRG-1 was also positively correlated with serum inflammatory factors including TNF-α, IL-1β, and IL-6.@*CONCLUSIONS@#Hypertensive renal damage mice display elevated expression of LRG-1 in serum and kidney, and irbesartan can reduce the expression of LRG-1 while alleviating renal damage. The level of serum LRG-1 is positively correlated with the degree of hypertensive renal damage, suggesting that it may participate in the occurrence and development of hypertensive renal damage.

Investigation of Pharmacodynamic Material Basis and Mechanism of Qianyang Yuyin Granules Against Hypertensive Renal Damage Based on LC/Q-TOF-MS and Network Pharmacology / 中国实验方剂学杂志

Objective:To systematically study the chemical components of Qianyang Yuyin granules and explore its main pharmacodynamic substances and mechanism in the prevention and treatment of hypertensive renal damage. Method:Liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （LC/Q-TOF-MS） was employed to comprehensively analyze the chemical components of Qianyang Yuyin granules. Agilent Poroshell 120 SB-C₁₈ column （3.0 mm×100 mm， 2.7 μm） was used， flow rate was 0.4 mL·min^-1， electrospray ionization （ESI） was applied and operated in positive and negative ion modes， the acquisition range was <italic>m</italic>/<italic>z</italic> 25-1 000. Mobile phase in positive ion mode consisted of water+10 mmol·L^-1 ammonium formate+0.125% formic acid+0.1% methanol （A）-［acetonitrile-water （9∶1）+10 mmol·L^-1 ammonium formate+0.125% formic acid］ （B）， and in negative ion mode consisted of water+10 mmol·L^-1 ammonium formate+0.1% methanol （A）-［acetonitrile-water （9∶1）+10 mmol·L^-1 ammonium formate］ （B） with the gradient elution （0-3.5 min， 5%B； 3.5-4 min， 5%-10%B； 4-9 min， 10%-25%B； 9-18 min， 25%-30%B； 18-25 min， 30%-50%B； 25-27 min， 50%-90%B； 27-32 min， 90%B； 32-33 min， 90%-5%B； 33-39 min， 5%B）. According to the information of the accurate mass， the multistage fragment ions， the mass spectrometric data of the standard substances and the relative reference literature， the structures of the chemical components in Qianyang Yuyin granules were identified. Based on the identified components， network pharmacology study， including target prediction and functional enrichment was applied to screen out the main active substances against hypertensive renal damage， and explore the potential mechanism. Result:A total of 99 chemical components were identified， from which 43 active substances and 48 key targets were screened out. The key components contained kaempferol， quercetin， ferulic acid， luteolin， caffeic acid methyl ester， cinnamic acid， aloe-emodin， emodin， gallic acid， <italic>N</italic>-<italic>trans</italic>-feruloyltyramine， isoorientin， 8-<italic>O</italic>-feruloylharpagide， ethyl caffeate， isookanin， cyasterone， 2，3，5，4'-tetrahydroxystilbene-2-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucopyranoside， loganin， alisol B-23-acetate and harpagide. The key targets included vascular endothelial growth factor A （VEGFA）， serine/threonine protein kinase 1 （AKT1）， Jun proto-oncogene （JUN）， etc. Conclusion:Qianyang Yuyin granules mainly exert the effects of removing heat from the liver， tonifying the kidney and removing blood stasis via modulation of vascular endothelium， angiogenesis， inflammatory reaction， oxidative stress， immune response and so on.

Research Progress of Astragali Radix and Salviae Miltiorrhizae Radix on Improving Renal Damage in Hypertension / 中国实验方剂学杂志

Hypertensive renal damage is one of the most serious complications of hypertension, and it is also the main cause of end-stage renal disease. Renal damage can further promote the rise of blood pressure and difficult to control, forming a vicious circle. Traditional Chinese medicine (TCM) considers that deficiency of the original and excess of the standard is its basic pathogenesis, and insufficient kidney-Qi and blood stasis are one of the most common syndromes of hypertensive kidney damage. Astragali Radix membranaceus is praised as the most important medicine for invigorating Qi, and Salviae Miltiorrhizae Radix is likened to "four things with the same function". Based on the theory of invigorating Qi and activating blood circulation, the effective ingredients of Astragali Radix membranaceus-Salviae Miltiorrhizae Radix are mainly astragaloside, Astragali Radix polysaccharide, mulberry isoflavone, salvianolic acid and tanshinone. Many studies have shown that in the process of hypertensive kidney damage, Astragali Radix membranaceu Its active ingredients, whether effective monomers, monomer compatibility or direct compatibility of drug pairs, can regulate blood pressure, reduce urinary protein, protect renal tubules, protect glomerular filtration barrier, improve renal hemodynamics and protect renal function by regulating multiple signal transduction pathways related to hypertensive renal damage. Lowering blood pressure and protecting renal function are two pronged functions. Based on the theory of Invigorating Qi and activating blood circulation, this paper reviews the research progress of Astragali Radix-Salviae Miltiorrhizae Radix in the treatment of hypertensive renal damage, with a view to providing scientific basis for the further study and clinical application of Radix astragali-Salviae Miltiorrhizae Radix in hypertensive renal damage.

The relationship of the genetic polymorphism of IL-6-174 and the response to benazepril treatment in patients with hypertensive renal damage / 天津医药

Objective To study the relationship between the genetic polymorphism of interleukine-6 (IL-6)-174 and the response to benazepril treatment in patients with hypertensive renal damage. Methods Two hundred and eighty-four patients with hypertension were enrolled in this study. The hypertensive renal damage was defined by the measurement of urinary albumin excretion rate (UAER). One hundred and sixty healthy subjects were enrolled simultaneously as control group. Blood samples were obtained from all the subjects, and plasma levels of IL-6 and the genotype of gene IL-6-174 were detected. The patients with hypertensive renal damage were treated with benazepril for 16 weeks. The responses were evaluated by the changes of UAER level to benazepril in different genotypes. Results Genotype CC was the most common of the gene IL-6-174 in patients with hypertension, followed by GG and GC successively, with the G/C allele frequency of 47%and 53%(P<0.05), while in patients with hypertensive renal damage, GG was the most common genotype of the gene IL-6-174, followed by GC and CC successively, with the G/C allele frequency of 68%and 32%(P<0.05). After benazepril treatment, the UAER was decreased most in patients with genotype CC, followed by GC and GG successively ( P<0.05). Conclusion The G allele frequency of the gene IL-6-174 is related with hypertensive renal damage in patients in Ningxia, with GG as the most common genotype. The patients with CC genotype have the best response to benazepril treatment, with most decreased UAER.

Effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats / 中南大学学报(医学版)

Objective To explore effects of fosinopril and losartan on renal Klotho expression and oxidative stress in spontaneously hypertensive rats (SHR) and the mechanisms underlying the protection against renal damage. Methods Fifteen male SHRs (22 weeks old) were randomly divided into 3 groups (n=5 in each group): a SHR group, a fosinopril group ［10 mg/(kg?d)］, and a losartan group ［50 mg/(kg?d)］. Age-matched Wistar-Kyoto (WKY) rats were chosen for a control group. Eight weeks later, tail arterial pressure, 24 hours urinary protein (Upro)，urinary N-acetyl-β-D-glucosaminidase (NAGase) were measured. Renal pathological changes were examined under light microscopy by HE staining. The renal mRNA and protein expression of Klotho were determined by RT-PCR, immunohistochemical staining or Western blot. The levels of total antioxidant capacity (TAOC), malondialdehyde (MDA), Cu/Zn superoxide dismutase (Cu/Zn-SOD), Mn superoxide dismutase (Mn-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined.Results The typical pathological characteristics of hypertensive renal damage were observed in the kidney of the SHR group．Compared with the SHR group, the systolic pressure, Upro, and urinary NAGase, the content of MDA and renal pathological damage was reduced while the renal Klotho expression and activities of TAOC, Cu/Zn-SOD, CAT, and GSH-Px were increased (P<0.05 or P<0.01) in the fosinopril or losartan group. There was no significant difference in renal Mn-SOD level among the 4 groups (P>0.05). Conclusion Fosinopril and losartan can exert protection against hypertensive renal damage through upregulating Klotho expression as well as reducing oxidative stress.

Correlation of tumor necrosis alpha and interleukin 10 with hypertensive renal damage / 中国综合临床

Objective To investigate the changes of the serum levels of necrosis alpha (TNF-o)and interleukin 10( IL-10 )in patients with hypertensive renal damage,and to study the correlation of TNF-α and IL-10 with the hypertensive renal damage. Methods Seventy three patients with primary hypertension were divided into two groups according to their urinary albumin excretion rate(UAER): simple hypertensive group( n = 37 ),hypertensive renal damage group(n =36). TNF-α and IL-10 were measured using radioimmune assay. Thirty normotensive healthy persons were selected as normotensive control group. Results TNF-α were significantly higher and IL-10 significantly lower in patients with essential hypertension than those in normotensive control group(TNF-α: [2.91 ±0.94]μg/L vs [0.98 ±0.35]μg/L,P＜0. 05;IL-10:[ 19.2 ±5.8]μg/L vs [28.6±5. 7] μg/L,P ＜0. 01 ) ,and in patients with hypertension,those with renal damage had higher TNF-α and lower IL-10 than those without( TNF-α: [ 3.75 ± 0. 88 ] μg/L vs [ 1.87 ± 0. 58 ] μg/L, P ＜ 0. 01; IL-10: [ 15. 4 ± 4. 3 ]μg/L vs [ 22. 5 ± 5.9 ] μg/L, P ＜ 0. 01 ), with statistically significant difference between groups ( P ＜ 0. 01 ).TN F-α and IL- 10 were found to have correlations with UAER ( r = 0. 703, P ＜ 0. 001; r = - 0. 613, P ＜ 0. 001 ),but no correlation with the level of blood pressure. Conclusion TNF-α increased and IL-10 decreased significantly in patients with hypertensive renal damage, which indicates that the imbalanced cytokine network may play a role in the pathological mechanisms of hypertensive renal damage.

The Protective Effect of Prostaglandin E_1 on Renal Tubules of Early Stage Hypertensive Renal Damage / 中国医师杂志

Objective To investigate the protective effect of prostaglandin E 1 on renal tubules of early stage hypertensive renal damage.Methods Forty-five patients were divided into two groups:Common treatment group who were treated with anti-hypertensive drugs,which were calcium channel blocking agents and angiotensin-converting enzyme inhibitors,and PGE 1 treatment group who were treated with both anti-hypertensive drugs and PGE 1.PGE 1 was given intravenously at dosage of 10?g per day. Two weeks after starting treatment,the urine alpha1 microglobulin(? 1-MG), N-acetyl-beta-glucosaminidase (NAG) and 24 hours total urinary proteins were examined in these two groups.Results After two week treatment, 24 hours total urinary proteins decreased in both groups, however, the urine ? 1-MG, NAG decreased only in PGE 1 treatment group (P