Abstract: Objective　To explore time-related changes in renal function, renal injury biomarkers, and renal pathology in rats entering a low-pressure and low-oxygen (LPLO) environment simulating moving from the plains to a plateau. Methods　Thirty male Sprague-Dawley rats were divided randomly into five groups (n=6 rats per group). Rats in the Control group were placed outside the chamber under normal pressure and oxygen conditions. Rats in the experimental groups were placed in an LPLO chamber to simulate a plateau environment at 5000 m above sea level, and were maintained in the chamber for 3, 7, 14, and 28 days, respectively. Serum levels of creatinine (CRE), cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) were measured as biomarkers of renal injury. Pathological changes in the kidney were observed by hematoxylin and eosin and periodic acid-Schiff staining, with quantitative assessment of the following parameters: average glomerular diameter, peritubular capillary (PTC) density per tubule, tubular injury score, and outer medulla (OM) congestion score. Results　NGAL, KIM-1, CysC, and CRE were significantly increased in the experimental compared with the Control group (all P<0.05). The average glomerulus diameter was significantly reduced in the LPLO 3 d group and significantly increased in the LPLO 14 d group (both P<0.05). The peritubular capillary (PTC)/tubule ratio was significantly decreased. The renal tubular injury and OM congestion scores were significantly increased (both P<0.05). Regression analysis showed that PTC/tubule was linearly negatively correlated with the LPLO duration, while CRE, CysC, and pathological indicators (mean glomerular diameter, OM congestion score, renal tubular injury score) were curvilinearly correlated with the duration of LPLO (all P<0.05). Variables with a curvilinear correlation were analyzed using restricted cubic splines(RCS). Each curve exhibited an inverted-L shape, with inflection points on day 7, indicating that the rate of increase of all indicators was highest within the first 7 days of LPLO, and the rate of increase then slowed from 7 days to 28 days. Conclusions 　A simulated move from a plains to a plateau environment was associated with significant structural and functional renal damage, but the kidneys then showed a self-adaptive adjustment process towards the plateau environment.

Abstract: Objective To investigate the effect of resveratrol (RSV) on the lymphotoxin analog ( LIGHT) / herpesvirus entry mediator (HVEM) pathway in rats with preeclampsia ( PE) and its protective effect on kidney injury. Methods Fifty pregnant Sprague-Dawley rats were randomly divided into 5 groups of 10 rats each: the normal group, PE model group, RSV low dose group (50 mg / kg), RSV high dose group (200 mg / kg), and LIGHT/ HVEM pathway blocker group (lymphotoxin beta receptor-immunoglobulin fusion protein [LTβR-Ig], 1600 μg / kg). All rats except those in the normal group were intraperitoneally injected with nitroso-L-arginine methyl ester ( 300 mg / kg, once daily for 5 days) to establish a rat model of PE. After successful establishment of the model, RSV solution was given by gavage to the rats in the RSV low and high dose groups, LTβR-Ig solution was injected via the tail vein to the rats in the LIGHT/ HVEM pathway blocker group, and the same amount of normal saline was given by gavage and tail vein injection to the rats in the Normal and PE groups. Each group was treated once a day for 5 consecutive days. After the last administration, 24-hour urine was collected and blood samples were obtained, and the serum creatinine ( Scr), blood urea nitrogen (BUN), and 24-hour urinary protein were measured as renal function indices using enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the pathological changes of renal tissue. Real-time fluorescent quantitative polymerase chain reaction was used to detect the relative levels of LIGHT and HVEM mRNA in renal tissue. Western blot was used to detect the relative expression levels of LIGHT, HVEM, nuclear factor kappa B (NF-κB), interleukin-6 ( IL-6) in renal tissue. Results Compared with the rats in the Normal group, those in the PE group exhibited pathological damage such as diffuse proliferation of glomerular endothelial cells and higher levels of Scr, BUN, 24-hour urine protein, renal tissue LIGHT mRNA and protein, HVEM mRNA and protein, and NF-κB and IL-6 protein expressions (P< 0. 05). Compared with the PE group, the pathological damage of renal tissue was alleviated in the RSV low dose group, RSV high dose group, and LIGHT / HVEM pathway blocker group; additionally, the Scr, BUN, 24-hour urine protein, renal tissue LIGHT mRNA and protein, HVEM mRNA and protein, and NF-κB and IL-6 protein expressions were lower (P< 0. 05). The changes in these indicators in the RSV high dose group were better than those in the RSV low dose group. No significant difference was observed between the LIGHT/ HVEM pathway blocker group and RSV high dose group (P> 0. 05). Conclusions RSV can inhibit the protein expression of the LIGHT/ HVEM pathway in renal tissue of rats with PE and improve PE-induced renal injury.

Abstract:Objective To investigate the protective effect and mechanism of action of Coptis chinensispolysaccharide (CCPW) on the kidney in a streptozotocin (STZ)-induced rat model of diabetes. Methods A Sprague-Dawley (SD) rat model of diabetes was established by intraperitoneal injection of STZ (60 mg/ kg). The diabetic rats wererandomly divided into disease model, high-dose CCPW (300 mg/ kg/ d), low-dose CCPW (100 mg/ kg/ d) and losartan(30 mg/ kg/ d) groups, containing 10 rats each. A group of 10 non-diabetic SD rats was included as the normal controlgroup. The rats were intragastrically administered the drugs once a day continuously for 8 weeks. At the end of the 8-weekadministration period, the effects of CCPW on body weight, kidney-to-body weight ratio, serum BUN and SCr levels, 24-hour urine protein levels, pathological changes in renal tissue, changes in the activity of the antioxidant enzymes SOD,CAT and GSH-Px, MDA content, and changes in the expression of IL-6, hs-CRP and TNF-α were observed in the diabeticrats. Results Compared with the disease model group, the CCPW-treated diabetic rats demonstrated a significant increasein body mass and a significant decrease in the kidney-to-body weight ratio. Significant decreases in serum BUN and SCrlevels as well as the 24-hour urine protein level were also observed. Pathological changes in the renal tissues of CCPW ratswere also less apparent, when compared with the untreated disease model animals. SOD, CAT and GSH-Px activity in renaltissues was significantly elevated, while MDA content and IL-6, hs-CRP and TNF-α expression in the serum weresignificantly reduced in the CCPW-treated groups. Conclusions CCPW may have a protective effect on the renal tissue of diabetic rats, possibly through its inhibition of oxidative stress and inflammation.

Abstract:Objective This study was designed to determine the effect of transient receptor potential vanilloid type 4(TRPV4) on angiotensin II(Ang II) induced renal injury in TRPV4-null mutant(TRPV4-/-) mice. Methods The mice were separated into sham group and Ang II-treated group. Ang II was infused systemically into wild type (WT) and TRPV4-/- mice for 4 weeks, and the sham mice were given with normal saline. Systolic blood pressure, urinary excretion of albumin and 8-isoprostane, serum creatinine, and the changes in renal pathology were assayed after 4-week treatment. Results Compared with the corresponding sham mice, Ang II infusion led to enhanced systolic blood pressure, increased urinary excretion of albumin and 8-isoprostane, increased serum creatinine (P<0.05), and enhanced glomerulosclerosis degree and renal tubulointerstitial injury index (P<0.05) in WT and TRPV4-/- mice. The results were associated with the enhanced collagen levels in the kidney (P<0.05). All of them were attenuated by the deletion of TRPV4 in the absence of alteration in blood pressure (P<0.05). Conclusions Deletion of TRPV4 could alleviate renal injury during Ang II-dependent hypertension, suggesting that TRPV4 may contribute to renal injury induced by angiotensin II.

Abstract:Objective This study was designed to determine the effect of transient receptor potential vanilloid type 4 (TRPV4) on angiotensin II (Ang II)-induced renal injury in TRPV4-null mutant (TRPV4 - / - ) mice. Methods The mice were divided into sham group and Ang II-treated group. Ang II was infused systemically into wild type (WT) and TRPV4 - / - mice via a miniosmotic pump for 4 weeks, and the sham mice were given with normal saline. Systolic blood pressure, urinary excretion of albumin and 8-isoprostane, serum creatinine, and the pathological changes in the kidney tissues were assayed after the 4-week treatment. Results Compared with corresponding sham mice, Ang II infusion led to enhanced systolic blood pressure, increased urinary excretion of albumin and 8-isoprostane, increased serum creatinine (P< 0.05), and enhanced glomerulosclerosis degree and renal tubulointerstitial injury index (P < 0.05) in the WT and TRPV4 - / - mice. The result were associated with enhanced collagen levels in the kidney (P < 0.05). All of them were attenuated by the deletion of TRPV4 in the absence of alteration in blood pressure (P < 0.05). Conclusions Deletion of TRPV4 could alleviate renal injury during Ang II-induced hypertension, suggesting that TRPV4 may contribute to the pathophysiology of angiotensin II-induced renal injury.

Abstract:Objective To provide a pathological model for the screening and study of drugs for the treatment of hyperuricemic nephropathy by establishing a reasonable and stable mouse model with hyperuricemic kidney injury. Methods By administering one, two, or three of five drugs, oteracil potassium, hypoxanthine, adenine, ethambutol, and yeast extract, a model was established with hyperuricemia renal injury in KM mice, at different modeling times by using different modeling doses and modeling methods. The changes in serum uric acid, urea nitrogen, creatinine, liver xanthine oxidase (XOD), and adenosine deaminase (ADA) activity were determined, and the variations in weight of each group were analyzed. Results Compared with the normal group, the serum uric acid level and urea nitrogen level in the mice significantly increased ( P < 0. 01) in the group with 1?day combination medication of hypoxanthine and oteracil potassium, the renal tubular type was abundantly observed in renal cortex, and salt crystals were abundantly observed in renal medulla. The serum uric acid level and urea nitrogen level in the mice increased significantly ( P < 0. 01), and liver XOD activity decreased ( P < 0. 05) in the group with 7?day combination medication of hypoxanthine, ethambutol, and oteracil potassium, and eosinophilic insoluble proteins were found in some of the proximal tubules of the renal cortex. The serum uric acid level, urea nitrogen level, and creatinine level in the mice significantly increased ( P < 0. 01) in the group with 14?day combined medication of yeast extract and oteracil potassium and the group with 14?day combined medication of yeast extract, adenine, and oteracil potassium. Renal tubular epithelial cells fell off in the renal cortex, and eosinophilic insoluble proteins were visible in some of the proximal tubules of the mice in the group with combined medication of yeast extract and oteracil potassium. Salt crystals were abundantly observed in the renal medulla of the mice in the group with combined medication of yeast extract, adenine, and oteracil potassium. The body weight of the yeast extract and oteracil potassium group increased faster than that of the yeast extract, adenine, and oteracil potassium group, with a significant difference between their body weights ( P < 0. 05). Conclusions Compared with other modeling method , the mouse model with hyperuricemic renal damage induced by the combined medication of yeast extract and oteracil potassium was more stable and its establishment had no significant effect on the body weight of the mice. Therefore, it is more suitable to use yeast extract combined with oteracil potassium once a day for 14 days to establish a mouse model of hyperuricemia renal damage.

Abstract:Objective To observe the effects of curcumin pretreatment on renal pathological changes and the level of oxidative stress in rats with various degrees of heat stroke. Methods Eighty male healthy SD rats were randomly divided into two groups (n =40): saline control and curcumin pretreatment groups. Each group was divided into four subgroups (n=10): 0 min (normal temperature), 50 min, 100 min, and 150 min groups in dry heat environment. Rats of the saline group were administered 0. 9% normal saline, and the curcumin group was administered 200 mg/ kg curcumin. The rats were treated continuously for 7 days. Rats of the 0 min group were subjected to room temperature, while the other groups were transferred to a climate cabin (The Simulated Climate Cabin for Special Environment of Northwest of China) under the conditions of 40. 5 ±0. 5°C and 10 ±1% relative humidity to establish the rat heat stroke model by a dry heat environment.The rats were anesthetized at the corresponding time points, and blood and kidney tissue were collected. The contents of creatinine and urea nitrogen in serum and superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA)activities in homogenates of kidney tissue were detected. Renal tissue was stained with HE, and pathological changes were observed. Results Pathological changes of renal tissue were aggravated by prolonged exposure to the dry heat environment. Pathological renal injury scores were higher in the saline group compared with curcumin pretreatment groups at the same time points ( P <0. 05, P <0. 01). The contents of serum creatinine, urea, and MDA were decreased in the curcumin groups compared with the saline group at the three heatstroke periods ( P <0. 05). The activities of renal tissue antioxidant enzymes SOD and CAT were increased in the curcumin group compared with the saline group ( P < 0. 05). Correlation analysis indicated that renal injury scores were correlated with MDA (r = 0. 75, P < 0. 01). Conclusions Curcumin pretreatment has a protective effect on rat renal injury induced by various degrees of heat stroke in a dry heat environment, and its mechanism may be mediated partly by antioxidant effects.

Abstract:To investigate the protective effect of Apocynin on acute renal injury after ischemia/reperfusion (I/R). Methods Acute renal ischemia/reperfusion injury in male SD rats was made by cutting right kidney and clamping left renal artery.SD rats were randomly divided into groups(sham-operated group, I/R group, I/R+ Apocynin groups). Serum creatinine was assayed by biochemistry.Renal morphology changes were observed by light microscope. The amount of monocyte were observed by immunohistochemistry.MDA was assayed by thiobarbiturate. GPx was assayed by DTNB. IL-1 was assayed by Enzyme-linked immunoadsordent assay. Result Compared with sham-operated group, Scr levels were significant increased in I/R group（P<0.05）,kidneys displayd significant histology changes in I/R group（P<0.05）, the amount of monocyte was significant increased in I/R group（P<0.05）, MDA and IL-1 were significant increased in I/R group（P<0.05）， GPx was significant decreased in I/R group（P<0.05）. Compared with I/R group, Scr was decreased in I/R+Apocynin groups, the amount of monocyte was decreased in I/R+Apocynin groups（P<0.05）, MDA and IL-1 were decreased in I/R+Apocynin groups（P<0.05）. GPx was increased in I/R+ Apocynin groups（P<0.05）. Conclusions Apocynin protect kidney against ischemia/reperfusion and accelerate recovery after acute renal ischemia/reperfusion injury,which may associate with the anti-oxidation and anti-inflammation