Advance on Chinese Medicine for Hypertensive Renal Damage: Focus on the Complex Molecular Mechanisms.

Hypertensive renal damage (HRD) is a major cause of end-stage renal disease. Among the causes of end-stage renal disease, HRD accounts for nearly 34% of the total number of cases. Antihypertensive treatment is primarily drug-based, but therapeutic efficacy is less effective and can have serious side effects. Chinese medicine (CM) has significant advantages in the treatment of HRD. CM is rich in various active ingredients and has the property of targeting multiple targets and channels. Therefore, the regulatory network of CM on disease is complex. A large number of CM have been employed to treat HRD, either as single applications or as part of compound formulations. The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system, antioxidation, anti-inflammation, rescue of endothelial function, regulation of vasoactive substance secretion and obesity-related factors, etc. This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.

Association between circulatory complement activation and hypertensive renal damage: a case-control study.

OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.

Expression of LRG-1 in mice with hypertensive renal damage and its significance. / LRG-1åœ¨é«˜è¡€åŽ‹è‚¾æŸå®³å°é¼ ä¸­çš„è¡¨è¾¾åŠå ¶æ„ä¹‰.

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-1ß, 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.

Qian Yang Yu Yin granule improves hypertensive renal damage: A potential role for TRPC6-CaMKKß-AMPK-mTOR-mediated autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Qian Yang Yu Yin granules (QYYYG) have a long history in the treatment of hypertensive renal damage (HRD) in China. Clinical studies have found that QYYYG stabilizes blood pressure and prevents early renal damage. However, the exact mechanism is not entirely clear. AIM OF THE STUDY: To evaluate the therapeutic effect and further explore the therapeutic mechanism of QYYYG against HRD. MATERIALS AND METHODS: The efficacy of QYYYG in treating HRD was assessed in spontaneous hypertension rats (SHR). Renal autophagy and the TRPC6-CaMKKß-AMPK pathway in rats were evaluated. The regulatory role of QYYYG in angiotensin II (Ang II) induced abnormal autophagy in rat podocytes was determined by detecting autophagy-related proteins, intracellular Ca2+ content, and the TRPC6-CaMKKß-AMPK-mTOR pathway expressions. Finally, we established a stable rat podocyte cell line overexpressing TRPC6 and used the cells to verify the regulatory effects of QYYYG. RESULTS: QYYYG alleviated HRD and reversed the abnormal expression of autophagy-related genes in the SHR. In vitro, QYYYG protected against Ang II-induced podocyte damage. Furthermore, treatment of podocytes with QYYYG reversed Ang II-induced autophagy and inhibited Ang II-stimulated TRPC6 activation, Ca2+ influx and activation CaMKKß-AMPK pathway. Overexpression of TRPC6 resulted in pronounced activation of CaMKKß, AMPK, and autophagy induction in rat podocytes, which were significantly attenuated by QYYYG. CONCLUSIONS: The present study suggested that QYYYG may exert its HRD protective effects in part by regulating the abnormal autophagy of podocytes through the TRPC6-CaMKKß-AMPK-mTOR pathway.

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.

The potential role of complement alternative pathway activation in hypertensive renal damage.

Hypertensive renal damage is a common secondary kidney disease caused by poor control of blood pressure. Recent evidence has revealed abnormal activation of the complement alternative pathway (AP) in hypertensive patients and animal models and that this phenomenon is related to hypertensive renal damage. Conditions in the setting of hypertension, including high renin concentration, reduced binding of factor H to the glomerular basement membrane, and abnormal local synthesis of complement proteins, potentially promote the AP activation in the kidney. The products of the AP activation promote the phenotypic transition of mesangial cells and tubular cells, attack endothelial cells and recruit immunocytes to worsen hypertensive renal damage. The effects of complement inhibition on hypertensive renal damage are contradictory. Although clinical data support the use of C5 monoclonal antibody in malignant hypertension, pharmacological inhibition in hypertensive animals provides little benefit to kidney function. Therefore, the role of the complement AP in the pathogenesis of hypertensive renal damage and the value of complement inhibition in hypertensive renal damage treatment must be further explored.

Polyphenol-Rich Extract from Litchi chinensis Seeds Alleviates Hypertension-Induced Renal Damage in Rats.

Litchi chinensis seed is a valuable byproduct of the subtropical fruit litchi (L. chinensis Sonn.), whose extract (LSE) has been confirmed to ameliorate dyslipidemia, hyperglycemia, and oxidative stress caused by type 2 diabetes. However, if LSE exerts an effect on anti-hypertension and hypertensive renal damage remains unknown. In this study, 13 polyphenols and one fatty acid were identified by UPLC-Q/TOF-MS. Network pharmacological analysis revealed that the therapeutic effects of LSE may be involved in multitargets and multipathways, such as the TNF signaling pathway, interleukin (IL)-6-mediated signaling pathway, NF-kappa B signaling pathway, removal of superoxide radicals, negative regulation of blood pressure, and so forth. Moreover, spontaneously hypertensive rats (SHRs) were daily gavaged with LSE (60 mg/kg) for 10 weeks. LSE remarkably reduced systolic blood pressure (SBP). The hypertension-induced renal damage was improved by suppressing inflammation and oxidative stress, which was consistent with the prediction of network pharmacology. In addition, LSE treatment remarkably increased the relative abundances of Lactobacillus and the production of short-chain fatty acids in the intestine. Our study indicated that a byproduct of litchi, namely, litchi seed, may be effective in reducing SBP and alleviating hypertensive renal damage.

Effects of Irbesartan and Amlodipine Besylate Tablets on the Intestinal Microflora of Rats With Hypertensive Renal Damage.

Objective: The present study aimed to investigate the effects of irbesartan and amlodipine besylate tablets on the intestinal microflora of rats with hypertensive renal damage. Methods: Eighteen 12-week-old male spontaneous hypertensive rats were randomly divided into three groups. The Ai-HDG group was given irbesartan at 15 mg/kg per day by gavage, the Ci-HDG group was given amlodipine besylate tablets at 1 mg/kg per day by gavage, and the Wi-HDG group, i.e., the control, was given the same dose of distilled water per day by gavage. The treatment lasted for 6 weeks. Six 12-week-old male Wistar-Kyoto rats were used as the reference group. Bacterial DNA was extracted from the feces of all the rats for high-throughput sequencing before and after the experiment. Operational taxonomic units were used to analyze the species of the intestinal flora, and the alpha diversity index was used to analyze the diversity. The relative abundance of the intestinal microflora in each group of rats was therefore analyzed at the phylum and genus levels. Results: Compared with the Wi-HDG group, the alpha diversity of the Ai-HDG group increased (p < 0.05), while in the Ci-HDG group, only the Shannon index increased significantly. At the phylum level, compared with the control group, in the Ai-HDG and Ci-HDG groups, Firmicutes (F) decreased, Bacteroides (B) increased, and the F/B ratio decreased (p < 0.05). At the genus level, compared with the Wi-HDG group, the Ai-HDG and Ci-HDG groups did not show a significantly delayed decline in lactic acid bacteria. However, in the Ai-HDG group, the relative abundance of Bifidobacteria increased. Conclusion: After the administration of irbesartan and amlodipine besylate, the disorder of intestinal flora in the rats with hypertensive renal damage improved. However, irbesartan was better than amlodipine besylate at improving the diversity of the intestinal flora in these rats.

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.

MicroRNA-200c-3p inhibits proliferation and migration of renal artery endothelial cells by directly targeting ZEB2.

Continuous activation of angiotensin II (Ang II) induces renal vascular endothelial dysfunction, inflammation, and oxidative stress, all of which may contribute to renal damage. It is well established that microRNAs (miRNAs) play crucial regulatory roles in the pathogenesis of hypertensive renal damage. However, the detailed mechanisms and regulatory roles of miRNAs as therapeutic targets underlying Ang II-induced renal artery endothelial cell dysfunction in hypertensive renal damage have yet to be fully elucidated. The present study aimed to explore the expression status and putative role of miRNA-200c-3p in mediating the progression of hypertensive renal damage. We carried out real-time quantitative PCR (RT-qPCR) to detect the expression of miRNA-200c-3p in rat renal artery endothelial cells (RRAECs) induced by Ang II. MTT and transwell assays were utilized to evaluate the effects of miRNA-200c-3p on cell proliferation and migration, respectively. The present results revealed that the expression of miRNA-200c-3p was significantly upregulated in RRAECs exposed to Ang II compared with that of normal cells. miRNA-200c-3p overexpression markedly inhibited cell proliferation and migration of Ang II-induced RRAECs. Furthermore, bioinformatics predictions and dual-luciferase reporter assays indicated that zinc finger E-box-binding homeobox 2 (ZEB2) was a direct target gene of miRNA-200c-3p and that ZEB2 expression was inversely correlated with the levels of miRNA-200c-3p in RRAECs after exposure to Ang II. The effects of ZEB2 silencing were similar to the inhibitory effects observed following miRNA-200c-3p overexpression, and recovered ZEB2 expression reversed the anti-proliferative and anti-migratory influence of miRNA-200c-3p upregulation in RRAECs induced by Ang II. The present study indicated that miRNA-200c-3p might suppress the proliferation and migration of Ang II-induced RRAECs by targeting ZEB2. The miRNA-200c-3p/ZEB2 axis will provide valuable insights into the clinical management of hypertension-related kidney disease.

Protective Effects of Combination of Radix Astragali and Radix Salviae Miltiorrhizae on Kidney of Spontaneously Hypertensive Rats and Renal Intrinsic Cells.

OBJECTIVE: To evaluate the effects of combination of Radix Astragali (RA) and Radix Salviae Miltiorrhizae (RS) on kidney of spontaneously hypertensive rats (SHRs) and renal intrinsic cells. METHODS: SHRs were intragastrically administrated with RA (5.09 g/kg) and RS (2.55 g/kg) either alone or with combination for 4 weeks; valsartan (13.35 mg/kg) was used as a positive control. Blood pressure and renal ultrasonography were monitored periodically. The biomarkers [microalbumin (mALB), cystatin ^C, angiotensin II (Ang II), interleukin-1 beta (IL-1ß), and ß2-microglobulin (ß2-Mg), etc.] in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA). The protein expressions [phosphorylated adenosine 5'-monophosphate-activated protein kinase-α1 (p-AMPKα1), sestrin-ß, calcium/calmodulin-dependent protein kinase kinase-ß (CaMKK-ß), phosphoinositide 3-kinases (PI3K), serine-threonine protein kinase 1 (AKT1), and vascular endothelial growth factor receptor 2 (VEGFR2)] in renal cortex were determined by Western blot. In vitro, the hypertensive cellular model was established by applying 2×10-6 mol/L Ang ^II. The primary human podocytes, human glomerular endothelial cells (HRGECs), and human proximal tubular epithelial cells (HK-2s) were pre-incubated with sulfotanshinone sodium (Tan, 10 µg/mL) and/or calycosin-7-O-ß-D-glucoside (Cal, 5 µg/mL). The cellular viability and apoptosis were assayed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Annexin V/PI staining, respectively. The level of endothelial nitric oxide synthase (eNOS) in culture supernatant was determined by ELISA. RESULTS: RA+RS signifificantly decreased the diastolic blood pressure, renal vascular resistance index, and parenchymal thickness, increased 24 h urinary volume as well as lowered the levels of urine mALB and serum cystatin ^C, IL-1ß and ß2-Mg of SHRs (P <0.05 vs. SHRs). The decreased protein levels of p-AMPKα1, sestrinß and CaMKK-ß and the increased protein levels of PI3K, AKT1 and VEGFR2 in renal cortex of SHRs were normalized after RA+RS treatment (P <0.05). In vitro, Tan and Cal attenuated the Ang II-induced abnormal proliferation and increased the apoptosis of HRGECs and HK-2s and improved the level of eNOS in culture supernatant. Whereas, neither of them showed powerful effect on podocyte. CONCLUSION: The combination of RA and RS had potential effects on alleviating the renal damages of SHRs and the renoprotection was independent of blood pressure level.

Amplified Association Between Blood Pressure and Albuminuria in Overweight Patients With Biopsy-Proven Hypertensive Nephrosclerosis.

BACKGROUND: An overweight person is at high risk for hypertensive renal damage. The effect of weight on the association between systolic blood pressure (SBP) and albuminuria remains unknown in patients with histologically diagnosed hypertensive nephrosclerosis. METHODS: A total of 97 patients with biopsy-confirmed hypertensive nephrosclerosis were recruited from 13 centers throughout Japan. We examined the relationship between SBP and proteinuria among those who were overweight, which is defined as a body mass index ≥25 kg/m2, and those who were not. We examined the interaction of weight and SBP with albuminuria at baseline and with the changes in estimated glomerular filtration rate (eGFR) during the observational period. RESULTS: Our results included mean age (54 years old), blood pressure (138/80), eGFR (53 ml/min/1.73 m2), and urine albumin levels (0.2 g/day). SBP was significantly correlated with log-transformed urine albumin levels (r = 0.4, P = 0.01) in patients who were overweight (n = 38) compared with patients who were not overweight (n = 59). Multiple regression analysis revealed that the interaction between being overweight and SBP with respect to albuminuria was significantly correlated with the log-transformed urine albumin level (ß = 0.39, P = 0.047) and was independent of age, sex, and potential confounding factors. The interaction between weight and SBP ≥140 mm Hg was significantly associated with a greater decrease in eGFR in the following 3 years. CONCLUSIONS: Being overweight may enhance susceptibility to hypertensive glomerular damage and may eventually lead to renal progression in patients with hypertensive nephrosclerosis.

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